It's a truism at the moment - and good news - that scientists in almost every branch of medicine see their research as "perhaps the most promising use of stem cells." Here, the Society for Neuroscience weighs in on what they see as the best and brightest stem cell research: "Embryonic stem cells have been shown to restore movement after paralysis. And with genetic engineering, stem cells can act as sophisticated protein delivery systems. Scientists have used them to deliver GDNF, a factor to aid in the survival of neurons targeted by Parkinson's and Huntington's diseases. Another team has used them to seek and destroy brain tumor cells. And a Norwegian group has proved that even in adults, neural stem cells have the power to become functioning neurons." Interesting times!
(From The Ledger). It's probably expecting too much for plain common sense to quickly penetrate the debate over social security and similar Ponzi-style wealth transfer schemes in other countries - especially given our current culture of entitlement. Still, it is apparently beginning to occur to some folk that radical change is necessary - or will be forced by circumstances. Unfortunately, bureaucrats are currently producing reports that greatly underproject future increases in healthy life span due to advances in medical technology. "Experts have repeatedly asserted that life expectancy is approaching a ceiling. These experts have repeatedly been proved wrong."
"DNA double strand breaks are regarded as one of the primary causes of cancer," says Kusch. "While there are natural mechanisms within an organism to detect and repair these breaks, factors involved in DNA damage repair must first bypass histones. Histones are proteins that condense DNA and protect it from mechanical and other stresses, but also make DNA rather inaccessible."
"These findings answer fundamental questions about DNA double-strand break repair," says Robb Krumlauf, Ph.D., Scientific Director of the Stowers Institute. "They may ultimately help to formulate new strategies of cancer therapy."
For more context on what we know and surmise about double strand breaks as related to aging and cancer, you may want to read a fascinating discussion between Robert Bradbury, Aubrey de Grey and Joao Magalhaes here at Fight Aging: Part One, Part Two.
Three items over at Betterhumans caught my eye today.
Testicles from newborn mice have yielded stem cells that could rival those from embryos in their treatment potential.
Japanese researchers led by Takashi Shinohara from Kyoto University report that they have established a line of potent cells from neonatal mouse testes using a special cell culturing method.
Two new trials have shown that a drug injected into the eye can effectively treat a potentially blinding form of age-related macular degeneration (AMD).
The wet form of AMD represents about 10% of the disease's overall prevalence but is responsible for 90% of severe vision loss. In wet AMD, abnormal blood vessels grow under the central retina and cause a progressive loss of central vision. This interferes with everyday tasks such as driving.
American bioethicists Arthur Caplan and Carl Elliott recently debated the issues in the open-access journal PLoS Medicine. Caplan is chair of the Department of Medical Ethics at the University of Pennsylvania School of Medicine in Philadelphia. Elliott is associate professor at the Center for Bioethics at the University of Minnesota in Minneapolis, as well as the author of Better than Well: American Medicine Meets the American Dream.
Ultimately, [opposition to enhancement] posits a static vision of human nature to which the [opposition activists] mandate we reconcile ourselves. If anything is clear about human nature, it is that this is not an accurate view of who we have been or what we are now, or a view that should determine what we become.
Quite aside from concepts of freedom and the merits of letting anyone control or restrict medical research and access to healthy life extension technologies (any such thing is hugely immoral in the libertarian worldview), Caplan has it right in his comment above. It is in our nature to change ourselves, to reach for what we can envisage. We can envisage longer, healthier lives and the technologies required to get there - those who stand in the way are guilty of prolonging death and suffering on an enormous scale.
BusinessWeek takes a high-level look at funding and progress in stem cell research in Asia: "The progress the Asians have made is 'astonishing,' says Robert A. Goldstein, chief scientific officer at New York-based Juvenile Diabetes Research Foundation International, which has teamed up with Singapore in funding ES Cell's efforts to find a cure for the disease." The authors views this as a competition - as do most of the participants and principles, no doubt - but a rising tide in medical science raises all boats. Successes in any country (and even business or competitive failures) in stem cell research still advance knowledge, capabilities and the potential for healthy longevity worldwide.
Boston.com is running a very readable article on the connections between biochemical and genetic mechanisms of stem cells and cancer. "Researchers know that [the cell signalling pathway called] Notch is active very early in the development of both zebrafish and humans, as the cells of the embryo decide what type of tissues to become. In most cells, it is then turned off. But recently scientists have found that cancer cells can activate the Notch pathway in adults' bodies, causing dangerous changes in their cells. This is apparently what happens in a rare form of leukemia called T-ALL. ... More and more, research is showing that messaging systems used early in development get turned back on and used by helpful stem cells in the adult body, and also by deadly cancer cells."
Prosthetics technology is undergoing advances every bit as revolutionary as regenerative medicine - in many ways it is another path to the same end goals. Diversity is always a good sign in technological progress; many divergent efforts are more likely to produce widely applicable results over the long term. EurekAlert reports on one small part of this ongoing process: "We plan to spend this $6.7 million to further develop technology that we hope will someday help blind individuals see, allow paraplegics to stand and eventually walk, and let people with vocal cord problems speak ... To go from a bundle of wires sticking out of somebody's head to a totally implantable system that is invisible will be a major advance in this technology."
Bruce Klein of the Immortality Institute has posted the latest in a series of previews for Exploring Life Extension, the film currently in production. This time it's an interview with Michael Rose, an evolutionary biologist known for his work on increasing the life span of fruit flies, amongst other things.
My major scientific focus over the last fifteen years has been experimental tests of evolutionary theories for the evolution of aging, fitness, life-histories, etc., on Drosophila melanogaster , although I collaborate with other investigators using different species. We have experimentally tested the general theory that aging evolves because of a decline in the force of selection with adult age.
The 2nd International Conference on Healthy Aging and Longevity will be held in Brisbane, Australia, March 2005. "This event is about providing leading edge, evidence-based knowledge on the achievement of increased human longevity and healthy/disability free life expectancy. It will explore the full spectrum of proven interventions including pharmaceutical, nutritional, clinical, educative, complementary, preventive and restorative means and the scientific underpinnings supporting them." The 2004 conference was well attended and widely regarded as a success. The presentations this year include a number of interesting healthy life extension topics mixed in with the more prosaic items.
A lot of very interesting and promising work is taking place at the forefront of medical research these days; stem cells, cancer therapies, gene therapies, and advances in bioinformatics have brought the prospect of cures for many previously untreatable conditions. How should sufferers go about researching the latest therapies and weigh the merits and risks of enrolling in a clinical trial? How does one even go about getting enrolled in a clinical trial or wading through the wealth of health information (much of it wrong or out of date) online? I receive a few e-mails on this topic every month, and so eventually wrote a short summary of my advice and suggestions - by no means exhaustive, but hopefully it provides a better starting point than a blank slate.
SFGate provides a good introduction to embryonic stem cells (ESCs) and their use in research: "the isolation of ESCs has opened up a rich variety of research opportunities. Among these are: the study of how cells assume their fate as part of one tissue or another; the exploration of birth defects and inherited disease; research on the origins of cancer; and the search for new therapies for numerous diseases. ... The passage of Prop. 71 has created the opportunity for California to proceed on human stem-cell research with unprecedented vigor. It is imperative that the opportunity be pursued with integrity and rigor. We are almost certainly going to be imitated. We should set a peerless example."
CNet is running an interview with Ray Kurzweil on the topic of his approach to healthy life extension.
His regimen for longevity is not everyone's cup of tea (preferably green tea, Kurzweil advises, which contains extra antioxidants to reduce the risk of heart disease and cancer). And most people would scoff at his notion that emerging trends in medicine, biotechnology and nanotechnology open a realistic path to immortality--the central claim of a new book by Kurzweil and Dr. Terry Grossman, a physician and founder of a longevity clinic in Denver. "I am serious about it," said Kurzweil, a wiry man with few lines on his face for a 56-year-old. "I think death is a tragedy. I think aging is a tragedy. And going beyond our limitations is what our species is all about."
The scoffing is something that we advocates must continue to work on - the science behind the path to much, much longer lives (if not immortality in the traditional meaning of the word) is very sound. Still, having serious people talk seriously about immortality is, I think, very good for the wider healthy life extension movement. It provides a much better outrageous extreme, a topic I explored a while back:
The middle of the road, "reasonable" position in public or political debate tends to gravitate to midway between what are perceived to be the two opposite outrageous extremes, regardless of the actual merits of any of these positions.
With this in mind, it is occurring to me that part of the ongoing problem in the modern political debate over healthy life extension is that our "outrageous extreme" has always been a tentative, reasonable proposal that medical research carry on and that near-term technology would seem to allow us all to live a little longer - say, to 150. When the outrageous extreme from the other side - from the Bush administration, Leon Kass of the President's Council on Bioethics, and others - is that no-one should be permitted to research ways of extending healthy life span, we can see that the average between these two positions is not very favorable to our future health and life span. We wind up where we are right now: anti-research factions in governments worldwide are restricting and legislating against all of the most promising fields of medicine, while attempting to force through complete bans on stem cell research, theraputic cloning and other promising technologies.
We need a better outrageous extreme.
When immortality is on the table for respectable discussion, proposals to significantly fund research into rejuvenation therapies and a cure for aging will be more successful.
You can read an illustrative excerpt from Ray Kurzweil and Terry Grossman's "Fantastic Voyage" over at the Longevity Meme.
(From Xinhua Online). A team of South Korean researchers have found a mechanism to explain why aging cells - with a reduced ability to proliferate - are more prone to becoming cancerous. This hinges on the same gene recently linked to grey hair and melanomas: "Bcl-2 barred the DNA repair mechanism, depriving the human body of a significant tool in countering mutations, dramatically heightening the likelihood of tumors appearing. ... Up until now, scientists have suspected cells accumulate mutations when they are young and become tumors when they are old. But we have learned aged cells suffer abrupt mutations due to a lack of DNA repair." How does this tie in with the link between short telomeres and cancer? More research is definitely called for.
Cancer research has been diversifying rapidly in recent years, the result of new technology and new knowledge. The International Herald Tribune reports on the latest new direction: "Within each tumor [lurks] a small population of elusive, highly potent cells that drive the tumor's growth ... In the past two years, cancer stem cells have gone from a theory on the fringes of biology to an idea that is attracting money and talent in cancer research. ... Most treatments today are judged by their ability to shrink tumors, but the new results suggest the size of the tumor is all but irrelevant: If doctors can kill the stem cells, the tumor is doomed, but if the stem cells survive, it will be back." Knowledge empowers scientists to develop targeted, effective therapies - we can hope this will happen here.
Biologists at the University of California, San Diego have found a fundamental mechanism used by embryonic stem cells to assure that genetically damaged stem cells do not divide and pass along the damage to daughter stem cells.
Their discovery, detailed in an advance online publication of the journal Nature Cell Biology, solves the longstanding mystery of how embryonic stem cells, which have the potential to divide an unlimited number of times and differentiate to make all of the cell types in the body, are able to avoid duplicating cells that have sustained genetic damage.
The scientists, who included Tongxiang Lin, a UCSD postdoctoral fellow and the first author of the study, and Connie Chao, a graduate student in Xu's laboratory, discovered that p53 activated by DNA damage in mouse embryonic stem cells directly suppresses the expression of a gene called Nanog, which is necessary for the self renewal, or unlimited duplication, of these stem cells. The suppression of Nanog promotes embryonic stem cells to differentiate into other cell types.
"The end result of all of these actions by p53 is to deprive embryonic stem cells with DNA damage the ability to self renew themselves and pass the DNA damage onto their daughter cells," says Xu. "p53 also contributes to the eventual elimination of DNA damage in the embryonic stem cells that have already differentiated into specific cell types, thus preventing the development of cancerous cells."
I'm sure that we can all think of a number of ways to make use of this information, assuming that the same mechanism is used in human embryonic stem cells. (This research used mouse cells, so it's fairly likely to be the same). You can find out more about the Nanog gene, uncovered in 2003, here:
The research group at the Institute for Stem Cell Research, University of Edinburgh, have shown that the Nanog gene, which is only expressed in pluripotent cells, plays an essential function in maintaining stem cells. Dr Ian Chambers who isolated the Nanog gene said: "Nanog seems to be a master gene that makes embryonic stem cells grow in the laboratory. In effect this makes stem cells immortal. Being Scottish, I therefore chose the name after the Tir nan Og legend."
A calorie restriction diet aims at reducing your intake of calories to 20-40% less than is typical, while still obtaining all the necessary nutrients and vitamins.
The Proceedings of the National Academy of Sciences has published an impressive set of statistics on the effects of calorie restriction (CR) in humans, based on ongoing US research. It makes for compelling reading: "It's very clear from these findings that calorie restriction has a powerful protective effect against diseases associated with ageing. [Practitioners will] certainly have a much longer life expectancy than average because they're most likely not going to die from a heart attack, stroke or diabetes."
Calorie restriction has been proven to extend healthy life span in most animals - including mice and primates - and the weight of evidence suggests that it does the same in humans.
A human study by John O. Holloszy, a professor of medicine at Washington University in St. Louis, published earlier this year noted that 18 people who had been practicing CR for three to 15 years showed dramatically reduced risk of developing diabetes or clogged arteries. ... It's very clear that calorie restriction has a powerful, protective effect against diseases associated with aging ... We don't know how long each individual actually will end up living, but they certainly have a much longer life expectancy than average because they're most likely not going to die from a heart attack, stroke or diabetes.
Calorie restriction has even been demonstrated to slow the progression of specific age-related conditions, such as Alzheimers:
Restricting the diets of mice reduces the build-up of plaques in the brain that are linked to Alzheimer's disease, according to a new study that offers further evidence of the benefits of calorie restriction. Obese people are already considered to be at a higher risk for developing Alzheimer's but the findings offer some insight into a possible explanation for this trend.
If you haven't already investigated calorie restriction as a means to a longer, healthier life, you certainly shouldn't wait any longer.
HealthDay reports that "many of the professionals who attended the ninth international conference on Alzheimer's Disease in Philadelphia this past summer predicted a viable treatment within the next 10 years." Alzheimer's research has been a priority for the NIA since the early 1990s; in many ways, the current state of public and private funding mirrors the the fight against cancer that commenced in the 1970s. The big difference is that it may take half as long and a fraction of the cost to win this war - one of many benefits of modern medical technology. Advocates for healthy life extension would like to see the same powerful engines of science, funding and public opinion turned to aging and serious anti-aging research.
Regenerative medicine encompasses many minor fields often overlooked by observers - such as how we fix broken bones. Betterhumans reports on the development of a new engineered compound that glues bones together and speeds healing. "Seliktar took fibrin, the protein in blood plasma responsible for clotting, and to it attached a synthetic material called polyethylene glycol that's a plastic used in biomedical applications ... "The result is a three-dimensional material with the biological properties of fibrin and the strength of plastic." These sorts of advances - enabled by materials science - may seem comparatively minor, but they greatly improve on natural regenerative processes and benefit many people.
Interesting that telomeres appear to play no role in either human skin aging, or bone marrow aging.
Aged skin was associated with thinning of the epidermis, decreased proliferation, and increased apoptosis below the granular layer. This was associated with increased epidermal expression of Fas and FasL. Telomerase activity was similar in aged and young epidermis. CONCLUSIONS: Fas/FasL-mediated apoptosis, along with decreased proliferation, may have a role in changes of human epidermis during ageing. Telomerase activity did not appear to be limiting in young vs. old human epidermis.
It is quite surprising that some major manifestations of aging such as skin and muscle atrophy can be reversed in old animals (or induced in young animals) by transplantion and/or joining of blood streams (parabiosis). It would be interesting to know how many signs of aging are due to immunological and systemic factors rather than tissue specific factors like telomeres.
We know that telomeres generally become shorter with age. We also know that errors in telomere mechanisms - much more common for shortened telomeres - are a root cause of many cancers. We know that telomere malfunctions are implicated in Werner's syndrome, an accelerated aging condition. Beyond this, the story seems to get much more complex - stay tuned.
You might want to read up on recent insights into the way in which the immune system deteriorates with age - scientists are closing in on the precise mechanisms by which this happens. This is a very promising sign for the prospects of future rejuvenative therapies for the immune system.
Randall Parker comments on recent discoveries relating to the way in which our immune system ages. "One subcategory of immune system cells may be aging more rapidly and causing most of the problem with reduced immunocompetence in the elderly. ... The authors show that old CD4 'helper' T cells cannot provide the stimulatory signals to B cells that prompt them to make antibodies. Old and young B cells, however, are equally effective if helped by young CD4 T cells." You might recall that researchers recently found that less useful CD8 T cells crowd out other types (such as CD4) as we get older. Understanding these processes is the first step on the path to fixing them - and thus rejuvenating age-affected immune systems.
While US states continue to debate public funding for stem cell research, groups in the UK are moving ahead with their own funding plans. The Guardian reports that "plans for a £100m fund to exploit medical discoveries from stem cell research are being developed by entrepreneurs and the government to launch next year. ... A key figure in the proposal is Sir Chris Evans, millionaire founder of Merlin Biosciences, now one of Europe's largest venture capital firms specialising in life sciences. He is seeking to raise £50m from the private sector to be matched by government funds." The objective for this fund is to accelerate the path from scientific discovery to fully commercialized therapy.
The Korea Times reports that researchers who successfully treated a paralysed patient with cord-blood stem cells are ready to start on a new round of trials as soon as their government gives permission. "We will conduct operations on two paralyzed patients as soon as the KFDA gives us the green light while the remaining two will also undergo stem cell therapy soon. ... For now, all is set for the second-round of tests, excluding the nod from the government as Song's team already secured matched umbilical cord blood stem cells for the patients and cultured them." Observers have been suggesting a healthy skepticism until the results of the first trial are repeated - here's hoping it works for other patients.
I received an interesting e-mail yesterday from a visitor to the Longevity Meme:
I am interested in your work on longevity and would normally support it. However, I have a real problem with your portrayal of the stem cell debate. Contrary to what is on your site, I believe most advances to date have stemmed [pun intended] from adult stem cells. You state the most promising advances are linked to embryonic stem cells and I believe that is untrue at this time.
I am very concerned about the push to use and create embryos for research and your position on this matter (both the factual claims you made which I believe are misleading) and the lack of concern over moral issues related to use of embryonic stem cells makes it difficult for me to wholeheartedly support or contribute to this longevity project. No doubt you would consider this a form of 'cutting the nose off to spite the face' but longevity is not everything. Any thoughts either on the relative contributions from adult vs embryonic? Any thoughts on how important it is to address the moral issues involved in embryonic stem cell research?
To which I made the following response:
I agree that my more commonly accessed static pages on stem cell research need to be updated on the topic of embryonic stem cell research - those pages tend to lag a little behind my evolving opinions, new science and the political debate. Comments like yours help to bump these items up the priority list.
You'll find a short synopsis of the important part of my position on embryonic research here:
In short, a collection of living cells has to be capable of feeling pain, be capable of thought, or be essential to the use of a meaningful amount of complex data amassed as the result of thought in order for it to have moral worth for me. Heritage and potential aside from these points count for nothing.
I am morally opposed to causing suffering in animals in the course of medical research, for example, but I don't see a meaningful alternative at the present time in order to avoid even greater human suffering - a suffering-free world is something we need to work towards in the long term, but you just can't do it all at once. The embryos used in stem cell research (small collections of cells without any meaningful differentiation) cannot suffer or feel, and are no different in this respect from any other non-essential cells taken from a human. You can probably extrapolate my opinions on other related topics such as abortion from these views.
Regarding embryonic stem cell research from a results-oriented point of view, it all comes down to a matter of time and consequences. I have no doubt that, even if hobbled and blocked at every turn, scientists will eventually understand how to turn any type of cell into any other type of cell - or create cells from scratch if need be. They will eventually understand how all of the most serious diseases do their damage at the genetic and molecular level. The relevant questions are how long it will take and how much very real, otherwise avoidable human suffering and death will be caused by delays - the death toll alone increases by 150,000 people each and every day.
The fastest way to understand cellular processes in order to cure many serious diseases is through embryonic stem cell research. Scientists use embryonic stem cell lines in order to understand the biochemical and genetic progression of many of these conditions - as well as to understand basic cellular processes that still remain a mystery. Adult stem cell therapies of the type being trialed now seem very suited to repairing certain types of tissue damage - but we know that because this research has not been blocked or suppressed to anywhere near the same extent as embryonic stem cell research. It is no surprise that adult stem cell research is far ahead, even in these comparatively crude first generation treatments.
(Although there is a good therapy in the works for spinal cord damage that uses embryonic stem cells:
This research group is aiming for human trials in 2006).
Embryonic stem cell research is very necessary; it is indeed essential for the most promising medical research of the next few decades. My comments above should serve to explain why I see this to be the case.
Insofar as we were talking about your support for increased human longevity, I would suggest that it is perfectly possible to support longevity research and serious anti-aging science while being opposed to specific activities within the broader research community. I certainly don't approve of everything that goes in the name of longevity research around the world, and nor am I representing a unified community voice in any way, shape or form. Finding a place in the community that you are happy with is a matter of finding the right groups to support and expressing your own opinions clearly and loudly.
What do you folks think? What needs to be updated or made more clear on my main pages on stem cell research?
Medical research often leads scientists in interesting, unexpected directions - so it is in the link between the graying of hair, stem cells and the skin cancers known as melanomas. An article at Betterhumans reports that "the loss of our youthful hues is due to the gradual dying off of adult stem cells that spawn a continuous supply of melanocytes, new pigment manufacturing cells. ... Melanoma tumors are caused by the uncontrollable growth of these cells and are hard to kill with treatment. ... what in the hair follicle is signaling the stem cells that is absent when aging occurs and the stem cells die off?" Researchers hope to be able to reproduce this mechanism of age-related death in cancerous stem cells.
Michael Cooper has generously offered to donate more than $23,000 to the Methuselah Mouse Prize for anti-aging research if enough additional donations arrive to push the final cash total above $100,000. If this happens, Bob Gelfond's earlier challenge will also be met and he will donate a further $5,000 to the cause. Only a little more money is needed to make all of this happen before the end of the year - I have pitched in and I hope that you can too. We're getting close, but still need a few more small donations to close the gap! This is a wonderful opportunity to make a few dollars go a long way towards building an effective initiative for serious healthy life extension research.
Welcome to another installment of "excess weight is bad for you," courtesy of CNN today: "There has been some suggestion that if you are particularly active, you don't have to worry about your body weight, about your diet. That's very misleading." A large study published in the New England Journal of Medicine reports that "women who were physically active but obese had almost twice the risk of death of women who were both active and lean. Women who were sedentary but slender were 55 percent more likely to die. Women who were both sedentary and obese were almost 2 1/2 times more likely to die." You have to take care of the basics if you want to live a longer, healthier life.
The transcript for the SAGE Crossroads interview with James Vaupel is now online. You may recall recent press on Vaupel's demographic research and suggestions that life expectancy in countries like the US could actually decline in years ahead. This interview serves to clarify his views and place those remarks in a wider context - Vaupel sounds like he agrees with the Reliability Theory of aging. Some excepts:
It used to be thought that there was nothing that could be done about aging, and that there was nothing that could be done to extend the length of life for humans.
But now we know that there is a lot that can be done about aging, and that people can live much longer than they used to live. So that's the plasticity of longevity.
That life expectancy is a measure of current conditions. It is not a prediction about how long somebody will live. But it's a measure of how long a person, a baby would live if that baby was confined to this year, could not get out of this year, was stuck with the conditions of this year.
So a more meaningful projection for most people would be, how long do we think that a newborn would live given mortality improvements?
The result is quite astounding. The result is that a newborn baby, in the developed world today - Europe, Japan, the United States - of those newborn babies, half will probably celebrate their hundredth birthday.
So the progress [in life expectancy prior to 1950] was largely due to saving lives below age sixty-five, especially children.
But after 1950 the improvements to life expectancy have largely been due to saving lives after age sixty-five, to this extension of life, to this giving - adding years to the life of older people.
So it's been a remarkable shift, and the shift has been due to the fact that since 1950 we've had various kinds of interventions that could help save people from heart disease, that could intervene with various infectious diseases that were killing very old people, so the antibiotics and so on helped older people a lot.
When Vaupel makes predictions, I think it's important to note that these are extrapolations; they do not and cannot take into account fundamental paradigm shifts in medical science. This is illustrated by any number of other competent, well-informed folks - such as Ray Kurzweil - making very different sorts of analytical predictions about the future of medical technology and human life span. The following pretty much says it all regarding extrapolation:
So when I'm criticized for saying that newborn babies will live to a hundred, I think the most powerful criticism is that I can't describe how they are going to live to a hundred. What's going to happen that will let them live to a hundred?
Then what I say is that I think heart disease death rates are going to come down. I don't know exactly how. I think we are going to find a cure or a way of preventing Alzheimer's, but I don't know exactly how. I think we are going to find ways of preventing or treating cancer, but I don't know exactly how.
So there are a lot of uncertainties about how this is going to be done. Basically, what I'm saying is that if life expectancy has gone up by two and a half years per decade for 160 years, it is likely to continue to go up. We are learning a lot about biomedical interventions, by health interventions. But I can't describe the details.
I have to say that I fall into the school of making it happen rather than the school of making projections. The capacity to influence the aging process is clearly not too far away under the right circumstances - getting there is a matter of finding the funding and will, and sooner is better.
Vaupel has a fairly sensible (if state-centric) view of the role of retirement in a longer life:
Well, there's a notion that's been developed mainly over the last hundred years, to separate life into three boxes. The first box you get educated, so you finish high school, you finish college, you finish graduate school and you are educated.
Then the second box is you work.
The third box you spend decades in forced leisure.
It doesn't make any sense to me to divide life up that way. But life has been divided up that way, and the number of people in most developed countries - once again, especially ... this is especially Europe - the number of people who are working after age sixty has fallen dramatically, especially over the last twenty years.
So people have sort of ... people have developed an assumption that they have a right to decades of leisure at age sixty or age sixty-five.
I don't see where this right comes from. People have a responsibility to contribute to society. We have to maintain the economy. If there are very large numbers of people who are not working at older ages, then that's going to be a burden on younger people.
I would have said "responsibility to support themselves," but we all know my leanings in that area.
One quote that jumped out:
Suppose you wanted to live to a hundred or I wanted to live to a hundred. How could we do it? What can you do? There is actually very little that an individual can do to extend an individual's life span by twenty years.
If the current human calorie restriction research continues to produce the same sorts of results as it has to date, then this lifestyle choice would seem to be a good shot at getting a fair chunk of those extra healthy years. Vaupel is right, however, in that what we have access to right now is pretty poor longevity medicine in the broader context of what is possible.
In summary, James Vaupel comes across as bullish on the prospects for increasing healthy life span through improved medicine - but he's in much the same ballpark as folks like S. Jay Olshansky or Richard Miller when it comes to the expected timeframe for these improvements. There are a fair number of other interesting items in there to find, so go and read the whole transcript.
The most interesting pieces of research have a way of turning up on sci.life-extension - the regulars there keep a good ear to the ground. In this case, the research in question is an examination of advanced regenerative capacities in a strain of mice:
The reaction of cardiac tissue to acute injury involves interacting cascades of cellular and molecular responses that encompass inflammation, hormonal signaling, extracellular matrix remodeling, and compensatory adaptation of myocytes. Myocardial regeneration is observed in amphibians, whereas scar formation characterizes cardiac ventricular wound healing in a variety of mammalian injury models. We have previously shown that the MRL mouse strain has an extraordinary capacity to heal surgical wounds, a complex trait that maps to at least seven genetic loci. Here, we extend these studies to cardiac wounds and demonstrate that a severe transmural, cryogenically induced infarction of the right ventricle heals extensively within 60 days, with the restoration of normal myocardium and function. ... The myocardial response to injury observed in these mice resembles the regenerative process seen in amphibians.
Understanding the process by which lower forms of animal life regenerate serious wounds has been a desirable goal for some time now:
Studies of expression profiles, functional assays, and cloning of mammalian orthologues of genes that promote regeneration are aimed at designing a molecular cocktail of genes and/or proteins that will reverse tissue damage and lead to regeneration from the body's own cells. The limb provides information that will lead to the regeneration of muscle, bone, skin, and nerves. The work on eye will help us regenerate lens, retina and optic nerve, and the studies of spinal cord to reverse paralysis.
It is interesting and potentially very promising that a similar regenerative process has been found in a mammal - indicating a much shorter, although still resource-intensive, jump to therapies that will work for human injuries.
Our laboratory has determined that the MRL mouse strain is unique in its capacity for regenerative wound healing, as shown by the closure of ear punches with normal tissue architecture and cartilage replacement reminiscent of amphibian regeneration as opposed to scarring. Furthermore, we have mapped the genes involved, identified a minimum of six different loci on five chromosomes, and shown that this is a complex multigenic trait.
Using this mouse strain in the present study, we show that the MRL heart, when injured with a cryoprobe, is capable of growing and replacing wounded tissue without fibrosis. We show that cardiomyocytes are capable of dividing near and filling the wound site with a mitotic index equivalent to that of amphibians. We also show that granulation tissue resolves quickly with restoration of normal myocardial architecture and a markedly reduced extent of scarring. Finally, myocardial function seems to recover from the injury.
(From Reason Online). Ronald Bailey on the theological and moral debate over embryonic stem cell research in the US: "Millions of intelligent people of good will maintain that seven-day-old embryos have the exact same moral standing as do readers of this column. Acting on this sincere belief, they are trying to block biomedical research on human embryonic stem cells that is desired by millions of their fellow citizens. ... Should we halt current human embryonic stem-cell research while these possible new avenues of research are being explored? Absolutely not. That would be surrendering to the moral bullying of a minority that wants to halt promising medical research that could cure millions on theological grounds that many of their fellow citizens do not share."
As our knowledge of biological mechanisms advances, reprogramming existing processes for new uses is proving to be a fruitful area of research. The BBC reports on efforts to convince the immune system to destroy the root cause of heart disease: "It works by priming the immune system to recognise types of cholesterol in the blood as foreign, so that it attacks and destroys them. New Scientist magazine reports animal tests by Sweden's Lund University found the jab could significantly reduce the build up of harmful deposits." This work is still uncertain and in the earliest stages, but it demonstrates that many potential uses can be found for each new technique added to the biomedical toolkit.
EurekAlert outlines a potential class of treatment for genetic diseases that would combine the regenerative properties of stem cells with gene therapy. Cystic fibrosis (CF) is a good testbed for this approach, as its symptoms are linked to a genetic defect in a relatively straightforward way: "[researchers] demonstrate for the first time that human bone marrow-derived adult stem cells can be coaxed to differentiate into airway epithelial cells and that encoding these cells with the gene that is defective in CF restores an important cellular function essential for keeping the airways clear of mucus and air-borne irritants." This is very promising work for the future treatment of a wide range of genetic conditions.
The Wisconsin Technology Network provides an update on proposals for a Wisconsin Institute for Discovery and state funding for stem cell research. "The response has been less than overwhelming to Governor Jim Doyle's proposal to invest nearly $750 million in public and private money in Wisconsin's biotechnology future. Budget-conscious members of the Legislature have choked on the price tag, opponents of stem-cell research have once again protested, and Milwaukee politicians have asked if they're being shortchanged in favor of Madison. ... Even though human embryonic stem-cell research was pioneered at UW-Madison, California's new Institutes for Regenerative Medicine could seize the advantage within a matter of years."
There is an opportunity for us all to help the M Prize for serious anti-aging research receive another large end of year donation. See the following from Methuselah Foundation fundraiser April Smith:
Michael Cooper would like to drive us above the $100,000 cash mark before the end of the year and is committed to donate $23,700 of NYSE stock to the Longevity Prize. He will do this IF we get what it takes to top the $50,000 mark in the Longevity Prize - which will trigger Bob Gelfond's $5,000 challenge funds. Reason is willing to put a $2,000 donation towards the Longevity Prize, all of which puts us in shouting distance.
The short of it is that we need only another $2000, but we need it fast. Between our own resources and those of our immediate friends in the life-extension world, I believe we can. Can you help?
Bob Gelfond's challenge was issued quite early in the history of the prize, and I'll admit that I wasn't expecting the chance to trigger it quite so soon. But onwards and upwards!
You might also want to take a look at this Immortality Institute thread on the donation challenge:
The short of it is that we need only another $2000, but we need it fast. Between our own resources and those of our immediate friends in the life-extension world, I believe we can. Can you help us relieve Michael Cooper of his precious stock before the end of the year runs out?
As I've said before.. I'm no millionaire but I believe strongly that it will take putting my money where my mouth is to encourage others to do the same, and it is only by action that we will see change, so I'm putting a $100 bucks in over and above my regular MPrize commitment. Anyone else?
So what are you waiting for? Pitch in a few dollars and help us net a large donation of stock for the prize fund.
It is good to see that the UC Riverside newsroom is covering the inaugural award of the Methuselah Mouse Rejuvenation Prize to biochemist Steven Spindler. From the article in question:
University of California, Riverside Professor of Biochemistry Stephen Spindler has received the inaugural Methuselah Mouse Rejuvenation Prize for his research in calorie restriction and its role in reversing aging in middle-aged laboratory mice, while extending their overall lifespan.
The aim of the prize is to speed the development of anti-aging interventions and promote public awareness of the prospects for them. According to a foundation statement, the research was "astounding because it worked on mice later in life."
According to Spindler's research, the fewer calories an animal consumes - provided malnutrition is avoided - the slower an animal ages and the lower the death rate from cancer, heart disease and diabetes. Spindler has served on several advisory groups and committees for the National Institute on Aging and National Institutes of Health.
He has been probing the life-extending effects of calorie restriction using advance gene chip technology, which is used to monitor and measure changes in gene expression. The major conclusions from his study are that many of the life-extension effects of calorie restriction happen rapidly and that these effects can be shown not only in young animals but also in older animals not previously on calorie restriction.
Spindler's intervention extended the average and maximum lifespan of the mice by about 15 percent and reduced the number of deaths from cancer.
News-Medical.net reports on an interesting advance in our understanding of stem cell repair mechanisms: "To regenerate unhealthy tissue, stem cells must first move toward the effected area. It had never been known how stem cells [are] able to home precisely to the site of injury or disease ... Using a simulated stroke model, the collaborators found that the chemokine SDF-1 alpha, secreted by injured or inflamed neural tissue, acts like an SOS signal and summons implanted human neural stem cells to the site of injury ... The stem cells appear to migrate to the site of an injury by engaging in a special kind of movement called 'chain migration' in which the cells slide and guide on top of each other, laying down a path for each other, much like a colony of ants moving from their nest to a source of food."
An article from the Daily Breeze contains a great quote from biologist Steven Austad: "I think people will someday live substantially longer than today. (Living) into your 100s will be fairly routine, up to 150 for the outlier (a longer-lived person who is the exception to the rule). I think this because we have been so successful at figuring out how to make animals live longer. The arguments (against appreciably longer life spans) are based so far as I can tell on ignoring a huge pile of research done over the past 15 years and the mystical belief that longevity, unlike every other human trait we know of, is impossible to change." The work of biogerontologist Aubrey de Grey is mentioned too - always a good thing.
Randall Parker has posted an excellent commentary on the "Polymeal" research that has been in the news recently. Given that it's only a matter of time before some yahoo in the anti-aging marketplace wades into the fray with Polymeal Inc., it's good to see a sensible view up front. "Note that the diet (assuming it works) would do this by delaying heart heart disease by an even greater number of years. A delay in the onset of heart disease would then allow time for other diseases to kill before heart disease developed to the point of being fatal. ... in order to get the benefit you would need to follow the diet for years, decades even. Also, if you already have very low cholesterol and low blood pressure I would not expect much of a benefit."
(From Newswise). Human trials are to begin for a regenerative therapy to regrow damaged cartilage in the knee. "When torn or damaged, the meniscus typically does not heal on its own, and the damaged portion is removed and not replaced. While current surgical techniques solve the short-term problem, osteoarthritis inevitably develops several years later." Via the new approach of "tissue engineering and biological stimulation through the implantation of a scaffold derived from pig intestines, we show the tissue where it needs to grow. ... In our animal studies, we have been able to grow back 90 percent of the meniscus on average." This is a good example of a simple, important repair for aging bodies made possible by the advance of medicine.
The Immortality Institute film project - a wide-ranging series of interviews with members of the healthy life extension community - is progressing well. I'm sorry to say that I missed my interview opportunity with Bruce Klein for the silliest of organizational errors on my part, but we will hopefully get that done the next time he is in the neighborhood.
The latest sample of work to date is a video interview with Joe Waynick, the CEO of Alcor, the well-known cryonics provider. Waynick has been instrumental in steering Alcor towards a much more professional, growth-oriented culture - I've said before that I believe this sort of change is essential for the cryonics industry. The industry serves a very necessary purpose:
Death is not a topic that people like to think about, and that is just as true of healthy life extension advocates as anyone else. We have to recognise, however, that the future of healthy life extension (regenerative medicine, stem cell therapies, understanding the biochemical processes of aging, and nanomedicine, to name a few fields) will not arrive soon enough to benefit everyone. Many people are too old, or suffer from other conditions that will kill them before cures can be developed. This is an unpleasant reality that we must face.
Do we just write these people off and forge ahead regardless? Of course not. Instead, we turn to the science and business of cryonics, a serious effort to solve this problem that has been underway since the early 1970s.
Cryonics is the only option for life extension open to many older and seriously ill people: those who cannot wait for the promised therapies of the next few decades. It is the science of placing humans and animals into a low-temperature, biologically unchanging state immediately after clinical death, with the expectation that advances in medical technology may eventually enable full restoration to life and health. A small industry of cryonics providers exists to freeze your body on death, in the hopes that future scientists (most likely using nanotechnology and nanomedicine) will be able to revive and repair you.
In order to serve this purpose for everyone who might want to take advantage of it in the future, however, cryonics must become much more progressional, grow, legitimize and publicize itself. This is not to demean the sterling efforts of many volunteers over the years, but for real growth, cryonics must move beyond volunteerism and amateurs - no matter how dedicated and skilled they might be. We can hope that this process is underway.
The Milken Institute is funding an effort called FasterCures, aiming to:
Evaluate the current systems of identifying and delivering cures
Identify barriers to progress that currently exist in these systems
Engage individuals and organizations in our mission to accelerate solutions
Create action plans to clear the path to faster cures
Clearing out the undergrowth of political, regulatory and protectionist parasitism that holds back scientific progress and its commercial application is a good thing for everyone, especially those of use who advocate healthy life extension and aging research. In our case, time is very much of the essence. Even the fastest plausible paths for future development of medical technology mean that meaningful rejuvenation therapies will come too late for many.
Still, it is a promising sign that an organization like FasterCures exists - it shows that recognition of the magnitude of regulatory and organizational problems in medicine has led to well-backed efforts to do something about it. I wish the FasterCures team the best of luck in achieving their goals.
This short piece presents another example of the continuing ripple effects caused by the passage of Proposition 71 in California. "Fearful the state will lose its edge in biotechnology research, two Democratic lawmakers will sponsor legislation next year to foster human embryonic stem cell research in Maryland. The bills ... would create a legal framework for conducting stem cell research. It would also provide state funds to underwrite research in a field that has inflamed passions in medical, scientific and religious communities." As Chris Mooney says, "In my view, thanks to what has happened in California, the debate in Washington hardly even matters any more."
The State reports on the state of progress towards using embryonic stem cells to heal paralysis. "Hans Keirstead is making paralyzed rats walk again by injecting them with healthy brain cells sussed from a reddish soup of human embryonic stem cells he and his colleagues have created. Keirstead hopes to apply his therapy to humans by 2006. If his ambitious timetable keeps to schedule, Keirstead's work will be the first human embryonic stem cell treatment given to humans. ... And he has an answer for those who say he's moving too fast and that his experiments with rats are dangling false hope before the 15,000 people paralyzed in the United States each year. 'This is extremely promising. Why the hell would we wait?'"
I'm very pleased to see the following press release. One of the many benefits of volunteering with the Methuselah Foundation is that I have early access to good news like this (before it makes it to the M Prize website, even).
Ammunition for the War on Aging - $100,000 sponsorship accelerator
British Visionary supports mission of Methuselah Foundation with large gift
WASHINGTON, DC For Immediate Release
On November 23, 2004, British entrepreneur David Fisher, learned that the first Rejuvenation M Prize - the prize for Rejuvenation and reversal of aging in middle-aged mice was awarded to Dr. Stephen Spindler. Impressed by the power of Prizes to accelerate investment in scientific research to reverse aging, Fisher decided to donate well over $100,000 in cash to the Methuselah Foundation which the foundation will use to accelerate its efforts to grow the M Prize fund.
"The biggest causes of suffering in the developed world are degenerative diseases, and by attacking the aging process itself, we can intervene in all of these simultaneously," said Fisher. "The Prize is obviously a model that works. Rather than funding only one group of researchers, it inspires scientists from all over the world to compete for the reward and recognition of a large, public prize. The success of the Ansari X Prize is an excellent example of this. I believe that the fundraising efforts that my donation will make possible will greatly increase the M Prize fund and most certainly bring about similar success."
Fisher has also joined the Three Hundred, a group of devoted individuals who have committed to donating $1000 a year for the next twenty-five years to the M Prize fund. Membership in The Three Hundred has climbed dramatically since the announcement of Spindler's success.
Fisher went on to say "People from all over the world have joined The Three Hundred. Their commitment shows that ordinary people are willing to make extraordinary sacrifices in their everyday lives and budgets in order to bring about the reversal of aging. I'm following their example and hope I will be an example to others to join so the prize can grow in size and power as quickly as possible."
Fisher's sponsorship is the first major donation to be given via the Methuselah Foundation's newly established affiliate in the United Kingdom. The Foundation's UK affiliate was established to provide tax deductibility for donations by citizens of the United Kingdom and to generally extend the Methuselah Foundation's efforts to advance Rejuvenation research and results into the international sphere.
The Methuselah Foundation will be adding more affiliate countries next year as it works to bring the strength of the international community to the cause - and to increasingly incite the competitive spirit of nations to substantially increase support and research into ending the diseases and suffering caused by aging.
For more information about The Methuselah Foundation, its M Prize competition and how to support the Foundation's mission, see www.MPrize.org or contact us via e-mail at firstname.lastname@example.org.
David Gobel : 202 306 0989 : email@example.com : http://www.mprize.org
Onwards and upwards, it seems!
Recent news has indicated that adult stem cells, at least, are increasingly used in regenerative therapies. This press release reports on using stem cells taken from the patient's fat tissue to aid regrowth of large portions of the skull: "The result of the case study does not tell us to what extent the osteogenic effect is directly attributable to the combination of techniques using stem cells compared to the effect of the bone grafting alone. However, the outcome provides encouraging anecdotal evidence on the potential application for these cells to treat difficult bone defects, laying the groundwork for future work in this area. After twelve months, subsequent to the submission of our findings, the patient continues to do well and the skull is stable."
A good overview article from PubMed looks at the the results of research into longevity genes over the past few years. (You can read the full version for free over at Science Direct). "This article reviews several genetic pathways that may extend lifespan through effects on aging, rather than through effects on diseases such as atherosclerosis or cancer. These include some of the genes involved in the regulation of DNA repair and nuclear structure, which cause the progeroid syndromes when mutated, as well as those that may affect telomere length, since shorter telomeres have been associated with shorter survival. Other potential longevity genes, such as sirtuins, are involved in regulating the response to cellular stress, including caloric restriction."
(From ScienceDaily). However it is that adult stem cell therapies - such as for heart damage - produce results, it does not seem to be the way scientists were hoping for: "Previous studies suggested that stem cells from bone marrow could be induced to become cardiac muscle, replacing damaged tissue and potentially restoring heart function. This series of more-rigorous experiments, however, found that the transplanted cells are unable to take the crucial final steps. They do not produce a muscle protein called sarcoglycan, which is necessary for normal heart and skeletal muscle function. ... It's clear that the transplanted cells aren't growing, as we once hoped, into heart cells, but they may stimulate the growth of new blood vessels into the damaged regions or they may secrete growth factors that promote recovery."
You may recall I mentioned research into the genetics of aging using kidney tissue a little while ago.
The findings, from different tissue groups within the kidney, suggest that the same changes in gene activity with age occur in all tissue types. This would certainly be hopeful news if verified - dealing with one type of process will require far less time and research funding than if there were a different process for every tissue type in the body. This "study doesn't suggest what factors drive the aging process, only that once it starts it follows the same path even in different organs ... whatever happens once aging begins, the mechanism that kicks off the process is probably genetically determined."
Randall Parker has followed up with his own more in-depth commentary:
The next obvious experiment would be to repeat this study with tissues from other organs and see if the same genes have changing levels of activity as tissue ages. Do some organs age at more rapid rates? Does this happen for everyone? One might expect some variability between humans due to genetic variants that accelerate aging in particular organs and also due to dietary habits and other habits that impose larger harm on certain organs (e.g. smoking on lungs or drinking on livers or fried meats on intestines).
Note that gene microarrays have gotten so powerful that these researchers were able to check the expression levels of all the known genes in a human cell. Chronological age is not always the same as age as measured by molecular genetic expression profile.
I'd love to see a longitudinal study where tissues are taken from a number of elderly people and assayed for gene expression to see if onset of diseases and mortality can be predicted from how far along the cells in a person seem to have aged according to gene expression levels.
As pointed out in that post, you can read the full paper online. Open scientific publishing is a very good thing; one has to hope that this new publishing model wins out over the established journal system.
Michael Rae recently joined The Three Hundred, a group of ordinary philanthropists who pledge to support the Methuselah Mouse Prize. He has written a moving, powerful essay on his thoughts and motivations: "The Three Hundred is a commitment to strongly and directly support what I believe to be the most effective vehicle for funding genuine anti-aging research - research that could drastically delay, or even ultimately eliminate, the slow, but gradually accelerating downward spiral of physical and mental deterioration with the passing of the years." You can read it here at the Longevity Meme - I hope that it will inspire some of you to put your best foot forward for the future of healthy life extension and support the Methuselah Mouse Prize.
A new study offers the following conclusions: "Restricting the diets of mice reduces the build-up of plaques in the brain that are linked to Alzheimer's disease, according to a new study that offers further evidence of the benefits of calorie restriction. Obese people are already considered to be at a higher risk for developing Alzheimer's but the findings offer some insight into a possible explanation for this trend." The normal cautions apply to extrapolating work on mice to humans, but researchers suspect that lowered blood glucose and insulin are good places to look for an explanation of this calorie restriction benefit. Isn't it time that you investigated calorie restriction? The health benefits are legion and its the only proven, available way to even modestly extend healthy life span.
The Washington Post has been running a series of online discussions in question and answer format for a while now. The latest features Chris Mooney and is entitled "Is Politics Stifling One of the Most Promising Avenues of Aging-Related Research?" It focuses, as you might expect, on the California research initiative and stem cell research politics elsewhere in the US. Some quotes:
As bioethicists David Magnus and Arthur Caplan wrote recently in the San Jose Mercury News, "While it is hard to tell from the media coverage in the wake of the presidential election, the citizens of California brought the stem-cell debate to a screeching halt. There will now be ample public funding for that research."
In my view, thanks to what has happened in California, the debate in Washington hardly even matters any more. Unless, of course, Senator Sam Brownback's bill to ban all forms of cloning--including "therapeutic cloning" or cloned embryo research--somehow passes the Senate. Then we would have a federalism showdown pitting the feds versus the Golden State, which has green-lighted this work. And at that point there are all sorts of interesting legal possibilities in terms of who would win...but barring that, I think Washington has been largely superseded in this debate.
The attempt to use the United Nations as a backdoor means of banning "therapeutic" cloning, or cloning for research, has failed for two years in a row now. Each time, defenders of the research have rallied and prevented such a misguided action by the UN. I think the people who have been fighting this fight are extremely relieved, and they don't expect to have to go another round any time soon.
Rather than a global treaty calling for a ban on all forms of cloning, the UN will instead be adopting a "declaration" on this subject. It will be the product of negotiation and, therefore, will likely contain language that pleases everybody. So, in short, this is a huge victory for supporters of research.
I don't expect more significant action at the U.N. anytime soon, then. In Congress the big possibility, as I've said before, is that Senator Sam Brownback's bill to ban all forms of cloning--including for research--starts to move.
As Chris Mooney points out, the danger of a Federal ban on therapeutic cloning still exists. This technology is vital to the most promising research into regenerative medicine - attempts to ban it are just as damaging as attempts to ban or restrict embryonic stem cell research. If you would like to make a difference to the future of medicine, health and longevity, you should contact your elected representatives and make your opinions heard.
The near future of medical nanotechnology is examined at Delaware Online: "All of biology is nano-scale. Nano means molecules; molecules are what we've studied in chemistry and molecular biology for generations ... Once we harness that ability to control molecules, the potential for medical applications are almost endless, say researchers." Early medical nanotechnology is likely to focus on diagnostics, nanostructures like the scaffolds now used in tissue engineering efforts, gene therapies and pinpoint drug delivery. Beyond that, however, the future of medical nanotechnology will rapidly become much more revolutionary. You can read more on this topic at Robert Freitas' Nanomedicine website.
Michael Rae explains why he has chosen to join The Three Hundred and offer his support to the Methuselah Mouse Prize for longevity research.
Copyright © Michael Rae.
Today, I made the decision to join The Three Hundred.
This essay will explain who The Three Hundred are, why I joined them, and why I think you should do so, too.
The short answer to all of the above is that The Three Hundred is a commitment to strongly and directly support what I believe to be the most effective vehicle for funding genuine anti-aging research - research that could drastically delay, or even ultimately eliminate, the slow, but gradually accelerating downward spiral of physical and mental deterioration with the passing of the years.
In other words, it is our best hope of substantially forestalling or escaping an otherwise-foreordained future of increasing disability, suffering and death - and of watching helplessly as our loved ones undergo the same terrible decline.
While I am still relatively young and believe that I am indeed aging more slower than those around me, I have suffered the loss of my loved ones to the aging process already. It's bad enough to watch allegedly "independently-living" aged strangers out in public, idly shuffling their feet, pushing cleverly designed wheeled walkers or balancing on their canes, unable to open the doors for themselves, faces a mask of apathy. It's much worse to spend even a few minutes in a nursing home, walking out of a world of relative health of body and mind into an asylum of decay: men and women, once fit and optimistic about the future, now tied to oxygen tanks, raving mad or sunk into almost complete retreat from the outside world, sitting down hours in advance of their meals for lack of any better purpose to their lives, needing help to get out of bed or clean their own wastes.
But what is truly terrible is to be in such a house of horrors to visit your grandmother - watching her become increasingly passive, disengaged, and helpless; seeing her unable to carry out the basic activities of daily living until she is a decayed funhouse mirror image of an infant, unable to walk or even control her own bladder; wondering when she will die, and whether that is really the worst fate that you can envision for her.
I am conscious that the advancing process of cellular disorder that took a young woman - a woman that escaped poverty in Scotland, worked through two World Wars to build a home and a family, bore my mother into the world, and cared for me through almost three decades as a mature, increasingly wrinkly, but still proudly independent gra'ma - and slowly sapped her in body and mind ... consciousness that these same processes are invisibly at work in my own flesh, and are now erupting visibly in my own mother and father.
Most people refuse to confront this reality. When the horror of aging is thrust in front of their noses, they push it away desperately, reflexively wrenching their attention toward another subject. They pretend that it is "not so bad," that it is unusual and will not happen to them, or engage in elaborate flights of intellectual apologism for the "natural," "divinely-ordained" order of things. They lie to themselves that they will be satisfied with just a few more years of life after which they will simply check out, well before the full weight of the years begins to crush them.
As even a cursory glance at previous generations would demonstrate, for better or for worse, no one will choose to give up life merely because their bodies are losing the powers and liberties without which they do not believe that they could live. Whether struck by aging or rendered paraplegic by a fall on the ice, they will grasp at the thread of life until their suffering is truly so wracking of body and soul that their will falters and they simply cannot go on. Fundamentally, we all want to live -- in youth and health if possible, in age and misery if necessary.
Many readers will know that I invest a substantial amount of my time and energy into the only scientifically justified method of delaying the horror of biological aging: calorie restriction (CR). It is a measure of my own horror in the face of the aging process that I spend so much of my life's energy in an intervention that I know perfectly well to be crude, weak medicine.
Tragically, those around me are so put off by the bitterness in the medicine that they refuse to take it. But even if they were to join me in massive salads and refusing Rocky Road ice cream, CR is not, ultimately, a solution to the problem. CR will - if, as I believe, the animal experiments translate well into the human case - buy perhaps a couple of decades of middle- and late-middle-aged relative health. It has already granted me improved vitality in many ways, even as it has come with a cost in other areas. But CR is just buying time - and not much time, at that. The specter of biological decay is still before me.
I want to live forever; or if not, I will accept as a second choice to live indefinitely in youth and in health. CR cannot deliver this dream. To do it, we will need a new biomedicine that attacks aging at its most fundamental, molecular roots, in ways that never naturally occurred in our genetic toolkit.
There is reason for optimism in thinking that this goal can be achieved. Decades of research into the biology of aging - much of it using the CR model - have revealed the fundamental molecular lesions that are associated with aging and almost certainly drive it. Theoretically, we could remove or neutralize these toxic wastes, creating interventions that will not just slow down the molecular gumming-up of life's machinery, but halt or even reverse it. We could actually undo the toll of the years ([1-4]; for a very accessible overview, see ), and then aging itself could come to an end. We would spend centuries or millennia in youth and health, only falling prey to catastrophic accident or disease.
There is significant progress toward [6,7] - and in some cases even preliminary proof-of-concept for [8-10] - several interventions based on these insights. The problem is to turn these as-yet-theoretical solutions - or any others! - into widely available therapies. As with any medical discovery, this entails a long process starting with test-tube studies and working hypotheses, moving to animal models, and finally progressing to human trials and regulatory hurdles.
Venture capital has demonstrated that it lacks the attention span or patience for such expensive, long-term projects in medicine. One major problem is that there is no way to quickly assess the effect of a new intervention on aging. You can perform a good rodent cancer study in a few months, and Phase II cancer trial work in humans can be accomplished in a year or so, but there's no way to do this with aging. The critical, absolutely essential first step - a full lifespan study in rodents - takes not five months, but five years, and requires many more rodent subjects (and proportionally greater expense).
As a result, all of the biotech companies that initially made their buzz by promising anti-aging drugs have retreated from this vision - more or less as soon as a putative anti-aging drug looks promising as a treatment for some diseases - and lifespan studies are abandoned. Geron, to pick the obvious example, was founded by Michael West to exploit telomerase as the cellular fountain of youth. Venture capital firms were initially excited: West put forward a powerful pitch during the early, optimistic inflation of the biotech bubble. Investors rapidly lost interest in long-term goals, however, and began insisting that Geron work to drugs (and revenue) into the pipeline post-haste. Thus telomerase the anti-aging enzyme became telomerase the target for cancer inhibition. The same thing has happened to Sirtris, Elixir, and all the way down.
Venture firms are not being terribly patient with some of the longer-pipeline ventures which do have obvious disease applications either: Advanced Cell Technology and even Osiris Therapeutics have been treading water financially for nearly three years now.
There are related problems in academic research, alas. For one thing, the length of time required to do a rodent lifespan study, and the nature of the experiment, makes it very unpopular with grad students and thus difficult for senior researchers to implement. No one wants to spend five years of an up-and-coming career minding lab rats in order to produce one single study (a survival curve, plus commentary) at the end. This is particularly true since, historically, these experiments have mostly been flops - not good material for inclusions in one's CV.
Another point worth noting is that government-funded researchers are not exactly at liberty to pursue whatever studies they want. Scientists must write funding proposals to explain exactly what they want to do, and exactly why. Here, a nasty vicious circle is in play: the people making funding decisions, while scientists, are first and foremost acting in their capacity as bureaucrats with political masters. Research thought to be fringe or misunderstood by politicians or the electorate - such as a scheme to "engineer negligible senescence" - is poison to a political or bureaucratic career. Ironically, because of its less cut-and-dried nature, similar bureaucracies in the arts (such as the National Endowment for the Arts in the US) are actually more insulated from their political masters - they can defend the allocation of funds to fringe or unpopular work on freedom of expression grounds, and because art is by its nature in the eye of the beholder. Neither defense applies for scientific work, of course.
Thus scientists continue to pursue relatively modest, uninspiring projects, and to couch their work in modest, uninspiring terms. "We're not looking for a cure for aging. We'd just like to learn how to delay some of the diseases of aging so that Granny can be more comfortable in her old age." This is what obtains funding, regardless of the actual limits on what is possible or plausible in medical research.
This state of affairs reinforces the impression, in the minds of the electorate, of a scientific consensus that real intervention in the aging process is impossible at this time. This reinforces the pressure on politicians to prevent government funding being "wasted" on such work. This in turn reinforces the need for scientists who want public funding to play it safe. Round and round this vicious circle goes...
How do we break out of this self-perpetuating system?
One way would be for people like us, concerned about aging, to fund the work ourselves: to hunt down projects that we consider likely to lead to extended life in mice, raise a huge pile of dollars, and just hand the money over to someone willing to do the study.
The Life Extension Foundations's LifeSpan study illustrates part of the problem with this approach. Having invested - to their credit - large sums of money in seriously testing a dozen or so promising supplements and drugs, they came away with a fistful of failed overlapping lifespan curves, a lot of dead rodents, and many, many millions of valuable dollars essentially wasted.
Another problem is sheer lack of funds - even funds to waste. For now, there are no huge, well-endowed research charities, nor nearly enough concerned individuals, contributing money to work on anti-aging interventions. Charities working on cancer and heart disease raise a lot of money - donors recognize these high profile diseases from which they suffer or of which their mothers, husbands and friends have died. Patients and their advocates are also very politically active in pushing for - and obtaining - public funding for work on their specific diseases. The present state of AIDS funding is perhaps the most spectacular and successful example of this form of activism, but the results of cancer and Alzheimer's advocacy are also impressive. Yet only a few people with the universal disease - aging - are prepared to make the same sort of effort. So long as people refuse to think of aging as a disease, as something that is not "a normal part of life," and as a medical condition that can be cured, then we will not see this kind of mass mobilization (or, in the case of AIDS, a mixture of an energetic and effective activist core coupled with widespread public sympathy and sense of urgency).
We have to come up with a creative way to mobilize the funds sitting amply in other coffers - the aforementioned government medical research bureaucracies and venture capital firms. From this starting point, we arrive quickly at the Methuselah Mouse Prize - http://www.mprize.org.
Structured as an improvement on the X Prize model, and enjoying that organization's Peter Diamandis as a chief advisor, the Methuselah Mouse Prize (or M Prize) actually consists of two related prizes. The Longevity Prize is to be awarded for the next record in single-animal lifespan in the laboratory mouse, the second Rejuvenation Prize for the greatest extension of lifespan in a mouse that is already elderly. The former will likely lead to advances in our understanding of the mechanisms of aging, while the latter is more likely to lead to viable anti-aging therapies for people who (as biogerontologist Aubrey de Grey once put it) have the misfortune of already having been born.
The M Prize has the potential to remove the stumbling blocks preventing scientists in government and industry from taking on the aging process as a curable disease. On the one hand, it reorients the incentives for industry. Right now, there is no specific incentive for private researchers to perform lifespan studies in mice: at most, they are a stepping stone toward long, expensive, human trials - and as noted, even the rodent studies are long and expensive. When a significant financial reward - and the promise of substantial publicity - is put in place, however, suddenly there is a business case for spending a few years rather than a few months in testing a compound in mice. Should you succeed in rejuvenating mice, you can bet that Big Pharma will be beating down your door for the rights to translate the intervention to the human case.
The M Prize can dislodge the vicious circle that drives the lack of serious anti-aging biogerontology in academic research. For the scientists, it creates an incentive to write those grant proposals, in hopes of obtaining more funding directly and greater prestige for their institutions - prestige itself tends to attract more funding. On the side of public opinion, the Prize structure, by its nature, captures public imagination and provides a dramatic way to educate the public and media that scientists are working on extending healthy lifespan in mammals. This increases the credibility of any similar reputable efforts and wins acceptance for the idea that it can be done in humans. In turn, changes in public opinion eases political constraints on awarding public funding for such projects - and may even lead to active pressure to make such awards.
The real tipping point, however, comes when aging is demonstrably reversed in an elderly mouse. Aside from the obvious point that success in mice implies a parallel success in humans with adequate further research, it may initiate a sea change in public opinion as people allow themselves to believe that aging could be cured in humans. I envisage this leading to a public and political demand for a War on Aging. At this point, the whole field of serious anti-aging research will become scientifically respectable. It will attract scientists and funding; this will further fuels the expectations of the public and pressure for public and private funding.
Before you know it, a virtuous circle has taken over from the vicious circle. Scientific results will drive public optimism, in turn driving political acceptability, public and private funding. Funding will eventually lead to the results we wish to see: breakthroughs in the science of longevity and aging.
The bottom line, however, is that breaking the existing vicious circle will require a substantial reserve of money, even if accomplished the efficient M Prize way. Here, again, we are confronted by the relatively small people who are willing to set aside their protective apologism for aging, and to recognize it for what it is: a degenerative medical condition no more worthy of respect and no more inevitable than syphilis. As I am sure many of you know, most people will not allow themselves to dream of an ageless future, or even acknowledge that it is desirable. Justification and peace of mind was necessary when nothing could be done - but that is no longer the case. Precisely because aging is universal, viewed as inevitable and "natural" because it happens after a relatively extended period of time, we don't see the sense of urgency or injustice that fueled the successful campaign to make AIDS a research priority in the 1980s.
To make it work, more of us are going to have to stop avoiding the issue and stare unblinkingly at the horror of aging. We must accept that aging is simply a medical condition, subject to research and treatment, and realize the magnitude of the moral obligation and personal stake resting in putting an end to biological aging.
To join The Three Hundred - named for a heroic force of 300 Spartan warriors who held back the invading Persian hordes at the narrow pass of Thermopylae, buying the Greeks time to mobilize an effective defense - is to commit to a donation of US$1000 per year for the next 25 years. The donations of the The Three Hundred will help build up the M Prize into an effort mighty enough to mobilize the scientific community into action for a concerted, all-out campaign to defeat aging and age-related disease.
The need is great for people to sign on to The Three Hundred - I have now answered the call. As you consider whether you, too, will step forward and make the financial commitment needed to fuel this critical change in the direction of aging research, bear several things in mind.
First, remember "you can't take it with you." You may think that you have an unusually well controlled case of aging, but it's still a terminal, degenerative disease. Even the best available treatment (calorie restriction) has some risky side effects associated with it. If a cure is not found, your fate will be sealed in a few short decades.
Second, this is a crucial time to contribute to the M Prize, as is begins to garner serious attention from the media and scientific community. You can help show the world that people are serious in the fight to cure aging!
Third, for every day of delay in the march towards a cure for aging, tens of thousands of people - men and women; parents, brothers, wives - will die. This is the daily body count resulting from biological aging. Can we really afford to wait?
We need an intervention that will fundamentally arrest, or reverse, the biological decay that creeps into our every cell with each passing year. Too few people are pushing this agenda. We - the healthy life extension community - must put our hands upon the wheel. If not us, who else, after all? We must wake up to the reality of an epidemic in slow motion: a medical condition rendered paradoxically invisible by its very ubiquity is slowly debilitating and killing us all. We should write to our politicians and legislators and demand they stop interfering with science and start working to support cures.
We must also realize that if we don't invest what we can to fight aging, this slow degeneration will take it all anyway. What value has money if our loved ones are dying in front of our eyes? What is the value of a dollar when wallets are emptied by the cost of fighting age-related disease as our bodies fall apart? What use are coins and notes when we have been trapped in the final stages of Alzheimer's? He who dies with the most toys is still dead - and likely received little pleasure from his toys in the gloomy final years of age-related illness and decay.
The success of the M Prize is not guaranteed - but as nearly as I can see, it is the only currently available way to make effective use of our resources to bring an end to the Gray Holocaust and commence an endless summer of healthy vitality. Time is growing short: we don't have many years or many chances to defeat aging.
Sign up at http://www.mprize.org . Give what you can. Your youth, your health, your life, your loved ones, and the future of humanity are riding on it.
1. de Grey AD, Campbell FC, Dokal I, Fairbairn LJ, Graham GJ, Jahoda CA, Porterg AC.
Total deletion of in vivo telomere elongation capacity: an ambitious but possibly ultimate cure for all age-related human cancers.
Ann N Y Acad Sci. 2004 Jun;1019:147-70. Review.
PMID: 15247008 [PubMed - indexed for MEDLINE]
2. de Grey AD.
An engineer's approach to the development of real anti-aging medicine.
Sci Aging Knowledge Environ. 2003 Jan 8;2003(1):VP1. Review.
PMID: 12844502 [PubMed - indexed for MEDLINE]
3. de Grey AD.
Challenging but essential targets for genuine anti-ageing drugs.
Expert Opin Ther Targets. 2003 Feb;7(1):1-5.
PMID: 12556198 [PubMed - as supplied by publisher]
4. de Grey AD, Ames BN, Andersen JK, Bartke A, Campisi J, Heward CB, McCarter RJ, Stock G.
Time to talk SENS: critiquing the immutability of human aging.
Ann N Y Acad Sci. 2002 Apr;959:452-62; discussion 463-5.
PMID: 11976218 [PubMed - indexed for MEDLINE]
6. Khan SM, Bennett JP Jr.
Development of mitochondrial gene replacement therapy.
J Bioenerg Biomembr. 2004 Aug;36(4):387-93.
PMID: 15377877 [PubMed - in process]
7. Gonzalez-Halphen D, Funes S, Perez-Martinez X, Reyes-Prieto A,
Claros MG, Davidson E, King MP.
Genetic correction of mitochondrial diseases: using the natural migration of mitochondrial genes to the nucleus in chlorophyte algae as a model system.
Ann N Y Acad Sci. 2004 Jun;1019:232-9. Review.
PMID: 15247021 [PubMed - indexed for MEDLINE]
8. Bendiske J, Bahr BA.
Lysosomal activation is a compensatory response against protein accumulation and associated synaptopathogenesis--an approach for slowing Alzheimer disease?
J Neuropathol Exp Neurol. 2003 May;62(5):451-63.
PMID: 12769185 [PubMed - indexed for MEDLINE]
9. Du H, Schiavi S, Wan N, Levine M, Witte DP, Grabowski GA.
Reduction of atherosclerotic plaques by lysosomal acid lipase supplementation.
Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):147-54. Epub 2003 Nov 13.
PMID: 14615393 [PubMed - indexed for MEDLINE]
10. Kass DA, Shapiro EP, Kawaguchi M, Capriotti AR, Scuteri A, deGroof RC, Lakatta EG.
Improved arterial compliance by a novel advanced glycation end-product crosslink breaker.
Circulation. 2001 Sep 25;104(13):1464-70.
PMID: 11571237 [PubMed - indexed for MEDLINE]
While California officials are working on building the California Institute for Regenerative Medicine authorized by the passage of Proposition 71, politicians in other states are considering, reconsidering and pushing for their own public funding. Here is a small sample of current activity around the US:
State funding for embryonic stem cell research could reach $10 million to $20 million, if Gov. M. Jodi Rell has her way. Rell wants to use state money to create a fund to help spur research institutions to finance studies in Connecticut. The governor wants to target biomedical research companies, universities and pharmaceutical firms. The fund would be "seed money" to match these interested parties.
State Comptroller Dan Hynes proposes a $1 billion bond issue over 10 years to fund the Illinois Regenerative Medicine Institute, which would distribute loans and grants to universities and medical research facilities in Illinois. The funds would pay for research involving embryonic, adult and cord blood stem cells. The effort is modeled on one in California, where $3 billion in public funding for stem-cell research will be set aside.
To pay for the bonds, Hynes has proposed a tax on elective cosmetic surgery, such as "tummy tucks," face-lifts and botox injections. A 6 percent tax would generate $15 million the first year if voters approve the plan in a statewide referendum in November 2006.
Under a plan proposed by state Rep. Phyllis Kahn, DFL-Minneapolis, Minnesotans' tax dollars could soon be used to pay for stem cell research at the University. Kahn said she plans to introduce a bill in the upcoming legislative session that would allow state money to pay for the University's stem cell research, including work on embryonic stem cells. The bill, co-authored by Kahn and several other Democratic representatives, is largely similar to the one she introduced last year.
Senator Kay Bailey Hutchison says Texas needs to pursue stem-cell research, and state leaders should work with Governor Rick Perry and the Legislature to develop a policy on stem-cell research. Hutchinson says it's necessary to keep the state from being -- quote -- "left in the dust by California.", referring to a landmark three billion dollar initiative to fund stem-cell research passed by California voters in November.
Leaving aside my opinions regarding the ultimately destructive nature of public funding (and the taxes and wasteful processes it requires), I would just like to point out that competition is a marvelous thing. Competition is the alchemy though which the basest of human motives are converted into shining towers of accomplishment.
The Australian reports on claims of an easy, reliable test that can detect early stage Alzheimers: "In patients with Alzheimer's disease, a gunky material called amyloid built up around nerve cells and seemed to interfere with the way they worked. Amyloid is thought to cause inflammation and damage to the tiny blood vessels that supply oxygen to the nerves. Researchers at the University of Melbourne found this blood vessel damage could be detected outside the brain, on the skin." The lack of a good diagnostic test for early stage Alzheimer's (and other neurodegenerative conditions) has been a real problem across the board. A test would make research move faster and better medical treatment possible.
(From EurekAlert). "Current treatments for Alzheimer's disease focus on the symptoms since no therapies have been clinically proven to slow or prevent progression of the disease. Amyloid protein deposits are present in the early phase of the disease - a fact that suggests a gene vaccination would be a step forward in slowing the progression of dementia." Potential Alzheimer's vaccines tested to date have been based on amyloid protein - and have some serious drawbacks. A Texas research team is now trying a new gene-based vaccine in mice to generate antibodies that fight the buildup of amyloid plaque without causing the known harmful side effects of existing vaccines.
Researchers say the study suggests that calorie restriction may lessen the natural loss of dopamine that occurs with age and may reduce the risk of developing Parkinson's disease. Dopamine is a chemical used by the brain to control movement.
Although dopamine levels in the brain decline naturally with age, this decline becomes accelerated in people with Parkinson's disease and causes problems with movement and uncontrollable muscle tremors.
Researchers say previous studies have shown that people who eat a low-calorie, low-fat diet and those who exercise appear to have a lower risk of developing Parkinson's disease.
The study showed that the calorie-restricted monkeys had higher levels of movement compared with monkeys fed an unrestricted diet. Levels of dopamine in the brain were higher in the monkeys fed the calorie-restricted diet. Those monkeys also had higher levels of a substance known as GDNF that helps dopamine cells survive longer.
Researchers say these preliminary results suggest that long-term calorie restriction may reduce the risk of Parkinson's disease by increasing the production of GDNF and preventing the destruction of dopamine cells.
The weight of science backing calorie restriction suggests that it is the best and easiest currently available method of improving your health and increasing your healthy life span. On the grand scale of what is possible, however, calorie restriction is just a small step in the right direction. This is why those of us who want to live well for far longer must do more than just take care of our own health - we must devote time and energy to ensuring that the healthy life extension medicine of the future arrives in time.
Wired reports on progress towards growing heart tissue for regenerative therapies: "The scientists used a pacemaker to produce electric signals that mimicked a heartbeat. The electrical stimulation was a key ingredient in growing the heart tissue quickly and getting all the cells to beat in unison, according to the researchers. They bathed the heart patch in a medium of nutrients and gases to keep it pumping, and eight days later, the cells developed into tissue similar to that of the native heart." Tissue engineering is moving forward. We're not there yet, but technology to repair age-damaged hearts is certainly high on the list of things scientists would like to develop.
The latest Longevity Meme article is a collection of excerpts from Gina Smith's "The Genomics Age", including discussions with biogerontologists Aubrey de Grey and Richard Miller. "When we finally are able to add significantly to our lifespans, we will look back and ask the moral question, why did we not do it sooner?" I'm always pleased to see more authors working to present a positive view of healthy life extension to the public: "We now know all the processes that make up aging well enough to target aging. And when you want to manipulate a complicated system, you only have to understand it a limited amount. You don't have to understand all of it. If we manage to triple the life expectancy of a fifty-year-old, we are pretty much there."
Leonid Gavrilov (noted for the reliability theory of aging) discusses the future at the Science Advisory Board. "Did you ever wonder how long will you be around and able to enjoy life? Or are you assuming that this question is irrelevant because you are not old? What do you think about the promise of forthcoming life extension offered by some scientists? Or perhaps you have more trust in an advanced discount-offer from your local funeral director? ... Pessimistic forecasts are usually flawed because of one hidden assumption [that] tomorrow will be more or less similar to what we have today. ... it is fundamentally flawed when applied to the progress in human knowledge and technology." You might find his Longevity Meme article on aging research and attitudes within the scientific community to be interesting as well.
Medical News Today reports on evidence for a type of multipotent stem cell in hair follicles that persists into adulthood. "Studies in the mouse showed that neural crest stem cells from adult hair follicles are able to differentiate into neurons, nerve supporting cells, cartilage/bone cells, smooth muscle cells, and pigment cells. Preliminary data indicate that equivalent stem cells reside in human hair follicles." If verified, this offers an easier path to regenerative medicine for a wide range of age-related degenerative conditions - trials over the past few years have already demonstrated the process of extracting adult stem cells, culturing and reimplanting them in the body.
Since I mentioned research into Werner's syndrome (a rare condition causing accelerated aging, or at least the appearance and consequences of accelerated aging) a couple of days ago, some interesting further work was drawn to my attention. It seems that gene expression changes due to Werner's syndrome closely resemble those accompanying normal aging:
Werner syndrome (WS) is a premature aging disorder, displaying defects in DNA replication, recombination, repair, and transcription. It has been hypothesized that several WS phenotypes are secondary consequences of aberrant gene expression and that a transcription defect may be crucial to the development of the syndrome.
Transcription alterations in WS were strikingly similar to those in normal aging: 91% of annotated genes displayed similar expression changes in WS and in normal aging, 3% were unique to WS, and 6% were unique to normal aging. We propose that a defect in the transcription of the genes as identified in this study could produce many of the complex clinical features of WS. The remarkable similarity between WS and normal aging suggests that WS causes the acceleration of a normal aging mechanism. This finding supports the use of WS as an aging model and implies that the transcription alterations common to WS and normal aging represent general events in the aging process.
Progeria, another accelerated aging condition, has already been confirmed to actually produce accelerated aging. If Werner's syndrome is also really accelerated aging, then understanding its mechanisms and finding a cure should help in the fight to defeat the normal aging process.
Enter Stage Right is running a review of Fantastic Voyage, the healthy life extension book from Ray Kurzweil and Terry Grossman. "As Kurzweil and Grossman point out, little changes like cutting down on the amount of salt and sugar in your diet or a moderate exercise program can do wonders for your health and longevity. Just as importantly they also evangelize the reader to take a proactive approach to their health ... Whether or not you make to 5000 years of age depends largely on whether the promise of new future technologies is fulfilled. In that sense Fantastic Voyage is an optimistic work, dreaming of a soon to be realized future where we will be able to rebuild our bodies and minds at will."
Excess weight is bad for your long-term health and longevity - all that additional fat works hard to damage your biochemistry over time. The LEF News reports on a study showing that obesity has much the same effect on ability to work and risk of disease as 20 years of additional aging. 20 years! "The study identified specific correlations between obesity and cardiovascular disease risk factors, and found that the health risks are the same as if the employees aged 20 years. Obese employees have higher prevalence rates of serious risk factors for cardiovascular disease." At the other end of the scale, it is suspected that some of the health gains resulting from calorie restriction stem from reduced weight and fat.
The court has finally issued a final judgment in the TW matter as it pertains to the rights of the nephews to examine the document of gift.
While we consider this judgment a significant victory, Alcor reserves the right to exhaust our legal remedies in this case and we will review the order with legal counsel to determine if further legal action is required prior to the December 30th deadline.
This judgment puts the TW affair to rest for now. However, that does not mean to say that John Heer will not try to come back with another attack.
As wrapped up as it gets in these matters, in any case. There is a real lesson here with regard to ensuring that your relatives are not going to try and destroy your cryopreserved body after death. If you're new to this story, you can use Google to find a wide range of articles and commentaries (biased in all directions) from various points in the drama.
Also worthy of note is the announcement of a new cryonics documentary in the works:
Alcor has given the green light for creating a high-quality documentary about cryonics. The documentary is being filmed in HDTV by a professional film crew and it is being produced by Debra Johnson, a professional producer with many years of experience in the television industry. This film will take a scientific approach to the subject of cryonics and it will contain many interviews with leading scientists throughout the industry. It will also contain member interviews and footage of the Alcor facility. The finished product will be made available to members to use as a recruiting tool. It will also be used on selected broadcast media stations to publicize Alcor and the field of cryonics.
This is a part of Alcor's new publicity and awareness program - a very good and necessary thing in my view.
Werner's syndrome is one variety of apparently accelerated aging. It is less aggressive than Progeria, the other most common varient of this class of rare conditions, but still horrible enough. Scientists have already shown that Progeria is accelerated aging (rather than just appearing to be accelerated aging), a fact that makes this condition even more compelling for aging researchers. Curing Progeria should pave the way for advances in our understanding of the aging process in healthy adults.
But back to Werner's Syndrome. An article from the ever-reliable Betterhumans brings us up to date on the latest:
A new discovery about a protein's role in a premature aging disease has given researchers a better understanding of the illness and provided insight into normal aging.
The disease, Werner's syndrome, causes young people who would be otherwise healthy to suffer from such aging-related conditions as osteoporosis, heart disease, cataracts, wrinkled skin and grey hair.
Sufferers are known to lack a protein called RecQ helicase WRN. However, until now scientists were unsure why the absence of this protein affected so many different cells.
Telomeres are like ticking clocks, normally shortening when cells divide and initiating cell death when they get too short. But without RecQ helicase WRN, Karlseder and colleagues found, telomeres can often be lost instead of just shortening.
The researchers believe that the lost telomeres can lead to chromosomal instability which can result in cancer. This could explain why many Werner's sufferers die of cancer by middle age.
"The finding that the loss of individual chromosome ends (telomeres) can induce cellular aging is significant for aging in general, since it contradicts the hypothesis that all telomeres in a cell gradually erode, and at a certain critical length induce an aging program," says Karlseder.
"The biggest implication of our studies lies in the understanding of age-related cancer development," says Karlseder. "One could hypothesize that avoiding individual telomere loss (by that I mean loss of a telomere from a single chromosome) would avoid genome instability and therefore cancer."
So it comes back to telomeres, just like many other threads of modern research into aging and cancer. Developing therapies for Werner's may bolster our understanding of telomere science, and thus aid the fight to cure aging and cancer.
TechNewsWorld takes a favorable look at The Scientific Conquest of Death, the first book of essays from the Immortality Institute. "A group of well-respected scientists and theorists take on the biological and philosophical arguments against radically extending the human life span. ... it is an entirely human response to try to fix problems that are harming people -- including death. Some 150,000 people die globally every day. ... it does seem rather odd that we aren't demanding a solution now. Perhaps one reason is that we live in a culture of death -- a culture that has convinced us that death is natural, good, and impossible to fight against, so we shouldn't even try. But we should try, and as this book shows, some very smart people are currently engaged in finding the solutions." And these folks need your support!
(From EurekAlert). Scientists are making progress in growing simple tissue and small replacement parts for the body. "A central feature of the [temporomandibular joint, or TMJ] is a thin sheet of cartilage about the size of a postage stamp that sits between the mandible and the skull. Called the TMJ disc, this sliver of cartilage cannot heal itself if it is injured or damaged. Approximately 70 percent of all TMJ disorders result from TMJ disc displacement, and there are no synthetic materials that can replace a damaged or injured TMJ disc. Rice's new TMJ tissue engineering program aims to develop methods for growing replacement TMJ discs that can be implanted without risk of rejection because they will be grown from a patient's own cells." This is a good step towards much more complex tissue engineering.
Aubrey de Grey (and others, like Chris Lawson) have suggested that radical life extension using technologies that could be attained in a matter of decades would lead to life spans of 5,000 years or so. Where does this figure come from?
Once our medical technology has passed the stage of what Aubrey de Grey calls acturial escape velocity - the point at which the effects of aging are being defeated faster than we age - our life spans will be limited only by accident and violence. The odds of death under these circumstances are very well researched for our current Western societies:
The odds of dying from an injury in 2001 were 1 in 1,781.
If you take the statistics for a healthy person in the prime of life and keep calculating the odds of death based on present day statistics, you wind up with a projected life span of thousands of years. As Chris Lawson says, it is perhaps more appropriate to consider ageless individuals to have half-lives in the same fashion as radioactive elements:
[An ageless man] who has lived 500 years has a 50% chance of living another 500 years. And should [he] survive that to reach 1000 years of age, he still has a 50% chance of living another 500 years. This is always true: no matter what [his age], he has a 50% chance of surviving another half-life.
(From the Union Leader). Like heart disease, diabetes is one of the first age-related conditions to be targeted by scientists working on stem cell based regenerative medicine. "Some of the first steps needed to fashion a true stem cell treatment for diabetes already have been taken. How stem cells might work for diabetics seems remarkably straightforward - in concept, if not in details. ... That is fueling intense research at many centers, including UCSF, where scientists are trying to discover the biological signals a stem cell needs to morph into an insulin-secreting cell. [Stem cells] could be a wellspring of transplant material for diabetics with no other options." More than just transplants too: stem cell medicine offers the possibility of full cures for this and other degenerative diseases.
You'll find a long, irreverent and fascinating profile of biogerontologist Aubrey de Grey at Popular Science today. The Methuselah Mouse Prize gets a good mention too: "One of the advisers to the Methuselah Foundation is no less a scientific entrepreneur than Peter Diamandis, whose X Prize helped wrap people's minds around another initially implausible idea, commercial spaceflight." While the author is overly skeptical the possibilities for near-term healthy life extension, he understands the value represented by scientists like Aubrey de Grey: "Aubrey is a cross between Svengali and a Methodist firebrand preacher, and yes, he can drive you up the wall. But in science, people like him are far too rare."
I'll give the Aubrey de Grey profile at PopSci a mention at the Longevity Meme tomorrow (wider human audience, fewer machine aggregators), but in the meanwhile here are some good quotes for you:
Aubrey de Grey's ideas are often met with skepticism, but, he says, "I haven't been thrown out of any rooms yet."
Aubrey de Grey has no victory pronouncements to make as of yet, but he is vigorously pursuing an even more challenging project. Using the legacy that Watson and Crick bequeathed us, he proposes to tinker with the essential biochemical pathways that drive the aging process. De Grey contends that we know enough to intelligently map out a program of anti-aging intervention research such that sometime in the next 100 years, and quite possibly much sooner, the average human life span may be 5,000 years, a figure brought short of outright immortality by the small number of people who will die from non-age-related diseases and everybody else who, given the boggling amount of time available to them on the planet, will eventually do something unlucky or stupid like walk in front of a moving rocket car. In de Grey time, the 400-year span between Shakespeare's England and today would be but the blink of an eye.
The key to this rosy scenario is a sort of biological Ponzi scheme that de Grey has dubbed "escape velocity." The idea is simple. If scientists can find ways to intervene in the cellular processes that cause our bodies to age - managing to keep middle-aged people alive an additional 40 years, say - that extra 40 years will buy enough time for biogerontological engineers to solve other damage problems before they emerge. Think of the body as a leaky boat. You don't have to keep it bone-dry to stay afloat; you just have to bail out the water at the same rate it's coming in. Or, as de Grey says, "You don't have to fix everything you're ever going to get. You only have to fix things in time."
Whatever else you can say about de Grey, he gives a good PowerPoint presentation. My favorite image from his bag of lectures is a chart that compares aging with fox hunting. Both are traditional, both are effective ways to keep a population down, and both are "fundamentally barbaric."
And sitting opposite de Grey and me at the Eagle is John Archer, a bona fide Cambridge professor and a leading authority on bioremediation, the use of microbes to clean up toxins in the environment. De Grey has sold Archer on the feasibility of identifying tenacious strains of bacteria in soil ("You can find bacteria that digest rubber," de Grey says), genetically modifying them for compatibility with humans, then delivering the bacterial genes to human cells to aid with the never-ending job of breaking down the metabolic waste that leads to macular degeneration (the leading cause of blindness in the elderly), heart disease and Alzheimer's. "It's sort of human engineering," Archer says. "It crosses boundaries, and that's exciting."
De Grey has carved a middle way between geriatric medicine and gerontology; he aims to reach what he calls "engineered negligible senescence." His is a pragmatic approach, he tells me emphatically over another pint, because by the time the gerontologists have cracked the mysteries of cellular metabolism, we'll all be worm's food. We're at an unprecedented time in the history of science, he says, having learned enough about the genetic and biochemical processes that lead to metabolic damage that we can begin to sketch out a plan to repair it.
The Methuselah Foundation gets a good mention too, as well it should. It's one of the most important initiatives in aging research advocacy currently underway. The full article is long - I could fill another few screens with good quotes, so get thee hence and read it all.
Two other related items are also up at PopSci:
We must intervene to halt these aging processes, says Aubrey De Grey. the rub is, no one has figured out how.
While most of us science-literate folks are watching the biotech revolution with tentative optimism, hoping for innovations like medicines that have no side effects because they're tuned to a patient's genes, or livers and kidneys grown to order for people with organ failure, some intrepid souls are taking much larger leaps.
SFGate takes a look at the legislative and legal details of Proposition 71: "Some laws are like a car patched together from spare parts, but the California Stem Cell Research and Cures Initiative is built like a tank. Lawyers involved in crafting the law said it was purposefully designed to barrel through all the political and financial obstacles that might hinder research in a field that backers believe could one day cure diabetes, spinal cord injuries, Alzheimer's disease and a host of other ills." Unfortunately this will make it even more prone to corruption and waste than the average government program. One is left having to trust the idealism of those in charge; not a welcoming prospect for the long term.
The Korea Times reports that researchers have identified a key gene controlling the natural process of neuron death. This opens up opportunities for new ways to treat neurodegenerative conditions: "If we prevent neuron apoptosis by controlling Bax's activities using medicine, we can increase the number of neurons and help treat Alzheimer's disease, Parkinson's disease and muscular atrophy, which are all caused from abnormal apoptosis of neurons in the brain ... For curing fatal diseases, many scientists have focused on stem cells concerning the creation of cells. But we started the research noticing that preventing the death of cells may also help treat diseases." A wide variety of approaches is always a good thing in medical research.
While I'm following up on items mentioned at the Longevity Meme, here is another one you (with thanks to Chris Mooney for pointing it out). This post goes into more detail on the science - what little we know of it at least - behind the latest Bioethics Council mutterings.
The first proposal might not yield any stem cells at all. If it did produce stem cells, they would probably be seriously defective.
The second proposal would probably yield only defective cells. Moreover, it looks like a solution to the problem only given a hokey and implausible view of what counts as an embryo.
So, alas, neither looks like a real solution.
Go and read the whole thing - there's a lot more leading up to that conclusion. I think my initial take in the Longevity Meme post was accurate; it's a fuss over abitrary definitions and bioethicists doing what they do best - trying to find ways to slow down the advance of medicine. The only problem here is that research in this field is neither free enough nor fast enough for those who are suffering and dying from conditions that could soon be treated.
In a way the TCE cells pose a problem similar to cancer. They divide too much and squeeze out cells that do necessary jobs. In another way the TCE cells are similar to the T cells that cause auto-immune diseases. They propagate too much to create antibodies that are not needed (in the case of TCEs) or even harmful (in the case of T cells causing auto-immune disorders). It would be interesting to know whether some auto-immune disorders are caused by TCE cells and whether people who suffer from auto-immune disorders have less diverse T cell populations.
In a way this report is good news for people suffering frmo auto-immune disorders because it focuses attention on the need to be able to very selectively eliminate large subsets of immune system cells. A therapy developed to eliminate TCE cells might also be adaptable to use against T cells that are causing auto-immune disorders.
Effectively the pool of people who need to have their immune systems selectively pruned back has just gotten a lot larger. This increases the odds of more resources being deployed to develop such therapies.
This treatment is a far greater economic value because it is of similar cost to existing treatments but works better because it actually fixes the cause of the problem.
Think about the economic value of stem cell treatments. Our problem in the United States isn't that we spend $1.6 trillion (as of 2002 - surely higher now) per year on medical care. Our problem is that so much of that care does not really fix the underlying causes of various medical conditions. Imagine medical treatments were capable of fixing everything that breaks just as auto mechanics can fix cars. Imagine you could therefore live in perfect health. Then I for one would not complain if that takes 15+% of the GDP.
What I find great about this report is that it shows that stem cell therapies that really fix what is wrong are moving into regular clinical practice. Stem cell therapies are not some distant prospect. They are happening now and every year that goes by from here on out we will have more stem cell therapies that successfully treat more diseases and disorders.
The economic argument is a good one (and I haven't been saying enough on that topic of late). The way to a healthier life is to greatly reduce the cost of curing and preventing disease. One way to achieve this end is to move beyond treating the symptoms of chronic conditions and repair the underlying problem. Medical research is expensive, but nowhere near as expensive as no medical research.
The President's Council on Bioethics has been generating some press recently with regard to their review proposed techniques for obtaining what are effectively embryonic stem cells without destroying embryos. William Saletan gives a better - if very biased - analysis in two parts at Slate. I agree with him that much of this seems to consist of word and definition games (or the result of arbitrary lines drawn in the sand) rather than anything of substance. For my part, I'd be happy to see bioethicists spending far less time and money in their attempts to slow down medical research for longer, healthier lives. Alas, we live in a time in which interference with freedom of research is widely accepted and supported. This is a real threat to our future health and longevity.
The continuing growth in knowledge of cellular mechanisms - and capabilities in bioinformatics - has certainly been paying off in cancer research over the past few years - good news for the future of healthy life extension, as cancer is big concern. Many potential cures are currently in the works. InfoAging reports on yet another promising new approach: "Scientists have fixed a defect in cancer cells that allows them to avoid the normal cell-death process, and as a consequence, they eliminated leukemia cells from laboratory mice. ... BCL-2 overexpression has been noted in many types of cancer, and was first found in lymphoma cells. ... This study provides strong support for the speculation that blocking BCL-2 would be lethal to cancer cells."
The latest seminar (Ken Dychtwald on "The Consequences of Human Life Extension") isn't up for download yet - and not having read much of him or his materials yet, I can't tell you whether he's on the side of light or darkness (or even really involved for that matter) in the anti-aging marketplace. Any of you folks who know more than I are welcome to educate me in this matter.
Last night, I went to the Long Now seminar with densaer. Ken Dychtwald on the consequences of human life extensions, and the like. Relatively short-term stuff, and relatively standard content, but he's a good speaker.
A press release at Newswise details an important advance towards controlled differentiation of embryonic stem cells: "The Johns Hopkins Medical Institution laboratory of John Gearhart has taken another small step on the road toward replenishing damaged cardiac tissue with pre-cursor cardiac cells grown from human embryonic stem cells (ES cells). Gearhart and his colleague, Nicolas Christoforou, here reveal preliminary data demonstrating what they say is a highly reproducible system for deriving cardiac progenitor cells from ES cells through controlled differentiation." Scientists are much further down the path of controlling stem cells than even a year ago - and this is the key to developing regenerative therapies capable of fixing age-related damage to our organs and tissues.
This PDF-format article on Aubrey de Grey and his Strategies for Engineered Negligible Senescence appeared in the Winter edition of Advances in Orthomolecular Research. It's a good read. "Late in the 1990s, this obscure computer scientist suddenly became obsessed with the enormity of misery and death caused by the aging process. But instead of raging impotently against age-related biological decay, he set out to do something about it ... Dr. de Grey earned his doctorate with a seminal work that overthrew previous thought on the role of mitochondria (the cellular 'power plants') in aging. But he eventually realized that even a solution to the problem of age-associated mitochondrial mutations would not lead to a final solution to the ongoing, seemingly-inevitable theft of health, dignity, and life by the aging process." His currently proposed solution took a few more years to gel into its present form.
The Houston Chronicle provides an itemized list of some of the more noteworthy public and academic embryonic stem cell research initiatives around the United States. Private research initiatives probably represent a similar level of expenditure, but never get as much press. Also noted are those locations that prohibit this and other promising fields leading to regenerative medicine: "Three states have old laws expressly prohibiting research on human embryonic stem cells: Nebraska, South Dakota and Louisiana ... Five states have new laws expressly prohibiting therapeutic cloning or research on cloned embryos: Arkansas, Iowa, Michigan, North Dakota and South Dakota."
People are fascinated by folks who make an effort to follow their own rules on appearance and mannerisms - so half of this Guardian piece is taken up with a discussion of Howard Trevor Jacobs' taste in clothing rather than the minor details of his research and acceptance of the Descartes prize. This fellow is one of the scientists organizing and contributing to recent important insights into the role of mitochondrial DNA damage in aging.
His multinational project, which involves scientists from Britain, Italy, Finland and France, promises not only to help in the creation of treatments for a host of illnesses, including deafness and diabetes, but to achieve the Holy Grail of medical science: a way to extend healthy human life.
Mitochondria are the power packs of the cell, with their own DNA, separate from the genes that direct the growth of rest of our bodies. As Jacobs puts it: 'Mitochondrial genomes are the cinderellas of genetics - you inherit them through the maternal line, and no one in science pays them much attention.'
Or that was the case. Thanks to work by Jacobs and other groups, it has been found that errors in mitochondrial genes can lead to the development of various inherited conditions, and that understanding their role offers an opportunity to correct these flaws.
Moreover, experiments using mice bred to accumulate high numbers of errors in their mitochondrial DNA produced startling results. The mice, aged less than a year, acquired a hunchback appearance. They also suffered from hair loss, osteoporosis, loss of fertility, heart disease and brain changes such as those seen in humans with Parkinson's disease.
In short, they got senile although only a few months old. 'This will lead to a much fuller understanding of ageing, and to rather straightforward ways of prolonging a healthy lifespan,' said Jacobs.
There are still some notes of caution to sound with respect to this work - just because you can produce what looks like accelerated aging in mice doesn't mean you have the keys to an extended healthy life span. The next step (already underway) is to build the tools needed to repair and regenerate mitochondrial DNA in mice. Then we can see if this a truly a path to greatly extended healthy life spans. Personally, I am cautiously optimistic - there is a fair weight of science behind the theories backing this sort of work.
One of the cardinal rules of large scale activism is not to let organization, effort and enthusiasm go to waste after the primary goal has been achieved. Yahoo! News reports that Proposition 71 backers have created the California Research and Cures Coalition (CRCC) with the aim of "educating opinion leaders, elected officials and policy makers, medical professionals, media and the general public about the potential for stem cell research, specific progress in the research fields and public policy developments. Beyond general education, CRCC intends to take a national lead in identifying and developing best practices and standards (medical and ethical) for stem cell research to help expedite discovery of cures and treatments for patients with chronic diseases and injuries."
(From News-Medical.net). Scientists at the Oregon Health and Science University have proposed an explanation for the deterioration of the immune system with age. "Throughout our lives, we have a very diverse population of T cells in our bodies. However, late in life this T cell population becomes less diverse ... [one type of cell] can grow to become more than 80 percent of the total [T-cell] population. The accumulation of this one type of cell takes away valuable space from other cells, resulting in an immune system that is less diverse and thus less capable in effectively locating and eliminating pathogens." Assuming this research is validated, work can now start on methods of balancing the cell population to prevent age-related immune system decline.
Betterhumans has been rolling out the good articles of late. Here, we have a possible biochemical explanation for some longevity benefits of exercise: "Perhaps some of the beneficial effects of exercise in human health are the result of the effect of AMP-1 activation on the aging process ... researchers found that by giving extra copies of the enzyme to nematode worms, the worms lived an average of 13% longer than controls. They also report that environmental stressors that activate the enzyme extend lifespan. ... This work supports our premise that aging is highly regulated and extends our list of molecular targets in pathways that affect lifespan by controlling metabolic processes." The work is from Elixir Pharmaceuticals, one of the companies currently pushing the aging research envelope.
Before getting to the latest mainstream articles, I should point out this excellent post from April. Highlights from a discussion of the Methuselah Mouse Prize at the recent Calorie Restriction (CR) Society conference:
We need a large amount of money, directed only at the actual prevention/reversal of aging. The problem with this is that nobody wants to fund it with venture capital because guess what... it takes a long time to see if people will die! As soon as a CR mimetic drug looks promising, for example if it looks like it can also be a cancer drug or some such thing, then all the capital goes into that, since a profit can be made right now, and the studies are shorter term.
So now we come to one of my favorites of de Grey's points: people are so convinced that stopping aging is impossible, that they don't even want to try. They're willing to put massive resources into searching for the cure for diseases, but when you start to talk about curing aging itself, people look at you like you just stepped out of a science fiction movie.
Questioner 1: "We all agree that we need to fund the research. I think we might be able to fund the real anti-aging research by generating interest in a normal, mainstream sounding foundation that will help people be healthy. We obviously need large, huge amounts of money. How can this be raised without appealing to a broader audience than life-extensionists like ourselves?"
Michael: "What we need to do is convince more people to believe that curing aging is possible, then get them to do something about it."
Questioner 2: "But Michael, what if you can't get normal people to believe that?"
Michael: "That's the whole point of getting people involved who know how to change other people's minds. It's going to take more than just scientists to cure aging... we have to mobilize the political will to fund the project. I believe we can do it... and April, people like you can play an important role. You have great skills at organizing, persuading, and supporting people in the formation of mass movements, even in the face of peoples' aquired defeatism and false consciousness. Not to make you personally responsible for changing the world or anything..."
There's lots more good stuff there for those of us who are advocacy-minded. Go read it all.
But on to the mainstream media. The BBC is collecting articles on aging science at a fair rate. Aubrey de Grey makes his case in the latest piece, facing off against the opinions of S. Jay Olshansky. Both have commented here on Fight Aging! before - in essence, their principle differences lie in the timescale of serious anti-aging research and the way in which science can and should interact with the media, new and old. This public discussion (and the less public discussion that goes on within the scientific community) has a great deal of influence on funding decisions.
Glenn Reynolds sums up a common, sensible response:
I don't know who's right, but I know who I hope is right.
What do we have to lose in a serious, go-for-broke medical Manhattan Project - private, public, or philanthropic - to understand and cure aging? Aside from money, that is ... and you know what they say about taking that with you.
The BBC feature was also mentioned in a Slashdot posting. Examining the comments made there and to a previous post featuring Aubrey de Grey is certainly an educational exercise for those of us who want to extend public support and understanding of healthy life extension. Aging and life span really are a strange sort of sacred cow in our societies - but we can't let that hold back or divert the possibility of creating technology to enable greatly extended healthy life spans in our lifetimes.
Lastly for the moment, here is a report at Samizdata of a talk given by Aubrey de Grey at a recent meeting of a UK transhumanist society. It focuses on the Methuselah Mouse Prize, perhaps the most interesting of Aubrey de Grey's current projects - at least from the perspective of those of us outside the scientific community. The Prize gives each and every one of us a way to contribute directly to the process of invigorating and expanding serious anti-aging research - that's a big deal, because that opportunity was not previously available to average folks like you and I.
You may recall that the Methuselah Foundation recently inaugurated its Rejuvenation Prize - this is a worthy effort that is continuing to grow.
James Hughes debates his transhumanist view of healthy life extension and advancing medical technology in a piece at Radio Netherlands. "We have to keep in mind that looking forward thousands of years the evolution of the human species and whatever its descendents may become is pretty incalculable. But in this century I think we are going to see some pretty dramatic changes. I think we will see the indefinite suspension of ageing by the end of this century. I think we will see quite dramatic accelerations of the potential of human intelligence in this century. We need to think about the consequences for society of an indefinite suspension of the prospect of death, barring accident."
Read interviews with some of the scientists working hard to extend our healthy life spans, reprinted with permission from Gina Smith's The Genomics Age: How DNA is Transforming the Way We Live and Who We Are.
Copyright © Gina Smith
Eighty and Loving It!
"Sixty Is the New Thirty" reads a cover of the AARP magazine, the one with the beautiful (and at the time of the photo, fifty-nine-year-old) Lauren Hutton on the cover. It is a breathless cover story and hardly scientific, but it makes you think. Thirty has been a magic number. Aristotle once said "the human body is at its best between the ages of 30 and 35." So if age 60 is the new 30, is 110 the new 80? Will it ever be? "It remains to be seen," says Leonard Poon, director of the University of Georgia Gerontology Center, "if you pass the threshold of, say, 120, whether you could be healthy enough to have a good quality of life."
To point, Madame Jeanne Louise Calment, the world's record-holding oldest person, lived to 122. But in the end, her family members were literally propping her up for interviews. Calment, however, lived independently well into her hundreds. Most centenarians, in fact, are even driving into their nineties and keeping up with lifelong hobbies. Is there a genetic reason for this? What do these old folks have that the rest of us may not? And is there a secret to prolonging youth, and not just years?
Old "youth" just seems to run in families, says Thomas Perls, a Boston University geriatrician who has been heading up the New England Centenarian Study, the largest DNA study ever of people age 100 and older. He is also a founder of Centagenetix, a Boston company that is hoping to find medicines to retard aging. He points to a photo of Sarah Knauss who, before she died in 1999, held title to being the oldest woman in the United States. She is pictured, at age 119, alongside her 95-year-old daughter, her grandson, her great-granddaughter, her great-great-granddaughter, and her great-great-great grandson. In all, six generations of Knausses sat still for a single snapshot. Pictures such as this will be increasingly common. The U.S. population now includes more than 40,000 souls age 100 or older. (In 1950, there were fewer than 2,300.) It is the country's fastest-growing demographic group.
"We are not trying to find the fountain of youth," Perls says. "If anything, we're trying to find the fountain of aging well." Most of the 750 participants in his centenarian study have aged well by any measure. "We have a small number of people, particularly guys, who do everything short of throwing an atomic bomb at their bodies and still live to 100," Perls says. They eat lots of fat and sugar. They never exercised. Some have been smoking multiple packs a day for half a century. (France's Calment had smoked filterless cigarettes for more than a hundred years of her 122-year life.) They even seem to age more slowly. If you look at pictures taken throughout their lives, you will notice that centenarians generally look younger than their peers at every stage.
Perls and fellow scientists say they are sure that these oldsters have genes that allow them to get away with things that would send most of us to early graves. But what are they, and where are they? In all likelihood, there is a vast network of genes that helps people live to extreme old ages, he says. Some genes may slow aging throughout life. Those genes have not been located, says Perls. However, a few age-related genes have turned up, according to his research. One lies smack in the middle of chromosome 4. Called the microsomal transfer protein gene, it appears to control how much cholesterol clogs up your veins. If you have this gene - one of the "genetic booster rockets," Perls calls them - you are more likely to live longer. While it isn't a switch that goes on and off, the mere presence of this gene does seem to appear in centenarians more often than in the general population. The gene may have the effect of limiting, or at least delaying, the onset of such age-related diseases as Alzheimer's, stroke, heart disease, and cancer, Perls says.
Jumpstarting the Search
"When we finally are able to add significantly to our lifespans," says Cambridge University geneticist Aubrey de Grey, "we will look back and ask the moral question, why did we not do it sooner?"
De Grey is perhaps the most outspoken biologist in the world. His Rasputin hairstyle and beard and his formal English demeanor belie his relative youth in this field - he is just forty years old. And he is an international rabble-rouser, a ruthless critic of the medical establishment's overly conservative approach to anti-aging. De Grey has made headlines with his claims that, outside of the fringe, venture capitalists and pharmaceutical companies aren't investing enough in anti-aging research. He says that's primarily because there's no short-term profit in it. "The funding isn't there," de Grey says. "But if we can do it in mice - significantly increase the years they are alive - this would be a result so impressive that it would trigger an immediate war on aging."
To this end, de Grey and colleagues have created the Methuselah Mouse Prize, named for the biblical figure claimed to have lived 969 years. In a prize potentially worth tens of thousands of dollars, scientists hoping to win must come up with the longest-lived laboratory mouse. (An alternate Methuselah prize will go to the late-intervention longest-lived mouse-that is, the mouse scientists waited until adulthood to treat.)
Getting a mouse to live to at least five years of age, instead of the normal two years, will be the first hurdle. Andrzej Bartke of the Southern Illinois School of Medicine managed to get his mouse, a genetically engineered critter named GHR-KO 11C (11C for short), to live 1,819 days, just short of five years. That is the equivalent of 150 to 180 human years. To accomplish this, Bartke engineered 11C with a gene that would limit the animal's production of insulin, leading to less age-related damage to the cells.
Once imaginations are captured, de Grey says he is optimistic about extending human lives to age 120 or even 130, within decades. "We now know all the processes that make up aging well enough to target aging," de Grey says. "And when you want to manipulate a complicated system, you only have to understand it a limited amount. You don't have to understand all of it. If we manage to triple the life expectancy of a fifty-year-old," he says, "we are pretty much there." That is, typically a fifty-year-old could expect to live another thirty years. If we could triple his or her remaining years, then science would have ample time to catch up with even better, longer-lasting treatments. The trick, he says, is going to be "repairing damage as it occurs."
An Engineer's Approach
Essentially, de Grey is advocating an "engineer's approach" to aging. Rather than trying to slow down the process of deterioration, you simply get better at fixing damage as it happens. This is the same as how you would keep an old house in good repair. You fix the roof when it has a leak; you paint the house when it needs it; you upgrade the wiring every few decades.
"This means that we should, in due course, be able to take people who are already middle-aged or more and rejuvenate them," says de Grey. "We will, in the first instance, only be able to do this imperfectly and incompletely, but that will be long enough to extend life span a bit. As time goes on, we will get progressively better at that. In fact, we will get better at an accelerating rate [as with all technology]. This means that eventually we will be getting better at fixing aging at a faster rate than time is passing. We will be encountering new things that go wrong with us at older ages, but we'll be fixing them faster than they arise." De Grey, to this end, has identified seven "strands," or areas of aging, that aging engineers might focus on in the future. They range from modifying genes to reduce the incidence of cancer to finding ways to replace cells that are lost to heart disease and Parkinson's.
"This might be difficult if it weren't for monkeys. They're fabulously similar to us and prone to age at least as twice as fast as us," de Grey says. "So we don't yet know what 200-year-old humans will die of, but we don't need to until we have some people that old-and by that time, we will for some time have had 100-year-old monkeys that we've been treating in just the same way that we treat ourselves: bad diets, no exercise, but all the life extension technology that we use on ourselves. And because those monkeys will have exhibited the same symptoms 200-year-old humans would, we'll have been working for a long time on fixing [those symptoms] in monkeys by the time humans get them. And when that occurs, we'll already know how to fix them well. By the time the first humans reach [age] 300, the same will be true by an even greater lead time. This all [depends] on the monkeys getting the same problems that we get, but at under half the age, but that's a pretty safe assumption," de Grey says.
According to de Grey's vision, eventually scientists will reach a kind of "escape velocity," at which point anyone with access to the latest medical care could live almost indefinitely. "At that point we will die only from accidents, wars, homicide, et cetera."
Slowing Aging Indefinitely
Richard Miller, a biogerontologist at the University of Michigan, has another perspective. "Most kids, when they are growing up, go through a phase where the idea of getting old and dying is really scary. . . . I did, too. And most people grow out of it, and I didn't. . . . If you're interested in scientific mysteries, things that aren't yet solved, where people really need to use their intuition to discover what the important cracks are, aging is right up there at the top of the list as cancer biology was fifty years ago or infectious disease was 200 years ago." While he agrees with de Grey that most scientists are too pessimistic about longevity research and more funds are desperately needed, he doesn't think fixing things that go wrong may extend life by enough of a margin. Research shows, he says, that the average woman would only live to age 95 if cancer, stroke, heart disease, and diabetes were fixable. But if you could slow down her aging - as some scientists have done with mice by restricting their calories to the level of a near-starvation diet - she'd probably survive to the age of 115, and would be basically healthy up until the end.
The idea that people can live longer as a result of a severely restricted diet is based on work done in 1935 at Cornell University. There, scientists discovered that calorie-restricted rats lived longer than rats fed regular diets. In the last sixty-five years, there have been hundreds of other studies showing similar results, and such organizations as the National Institute on Aging (NIA) spend several millions of dollars a year on related research. The calorie-restriction longevity technique may work because it lowers blood sugar levels, but scientists say they don't advise it for humans: It tends to make people miserable. However, a drug that duplicates the effect of lowering blood sugar is an oft-cited goal among anti-aging specialists.
"In general, I like the idea of fixing things," says Miller. "If someone has a broken arm, a cast is in order, and if someone has cancer, taking it out is a good idea. But in my view, none of this has much to do with aging research. So many things go wrong, more or less at the same time, in old individuals [such as two-year-old mice, ten-year-old dogs, and seventy-year-old people), that the notion that one can somehow fix all of them seems wrongheaded to me, particularly because at this point we don't have any really good ideas about how to stop any of the key problems-cancer, Alzheimer's, diabetes, heart attacks, hip fractures, and many other problems."
"The nice thing about anti-aging interventions," Miller continues, "is that, like caloric restriction and some genetic mutations, in unknown ways these postpone or retard nearly all of the adverse effects of aging at the same time. So I think it would be a good idea to learn more about how aging works to produce the diseases and disabilities of old age so that we could, potentially, figure out how to delay this process and stay alive and healthy for longer."
Miller agrees with de Grey that one of the biggest problems facing aging research is a lack of funding. "I think that if it were politically feasible to devote to aging research the same kind of funding that has gone into Alzheimer's disease research, or into AIDS, or into breast cancer, or 10 percent of the money that goes into the purchase of cosmetics - $45 billion per year in the United States - we would, in twenty to thirty years, have some pretty good ideas about how to delay aging in people," says Miller. "Actually testing these approaches in people would take a generation, though testing them in pets [dogs, for example] would be a good deal quicker."
An Unexpected Obstacle For Anti-Aging Research
As you've seen, biogerontologists are all over the map in their theories for what exact treatments will work to delay aging and lengthen human life. But one of the biggest obstacles they face is the attitude people have toward the research. Biogerontologist Richard Miller calls it "gerontologiphobia."
"There is an irrational public disposition to regard research on late-life diseases as marvelous, but to regard research on aging, and thus on all late-life diseases together, as a public menace bound to produce a world filled with nonproductive, chronically disabled, unhappy senior citizens consuming more resources than they produce," Miller says. The same arguments were made 200 years ago, against penicillin, surgical anesthesia, and plumbing systems, he adds.
According to Aubrey de Grey, "[T]here's the plethora of arguments why curing aging might not be a good idea . . . but that's just a crutch to help people not get worked up about the perceived infeasibility. They'll be forgotten overnight when big progress is realized . . ."
The BBC interviews biogerontologist Aubrey de Grey: "Ageing is a physical phenomenon happening to our bodies, so at some point in the future, as medicine becomes more and more powerful, we will inevitably be able to address ageing just as effectively as we address many diseases today. I claim that we are close to that point." The opposing point of view is provided by in an essay by S. Jay Olshansky - regular readers will know by now that I'm backing Aubrey de Grey in this debate over feasibility and timelines. If you haven't yet taken the time to read the material at the Strategies for Engineered Negligible Senescence and Methuselah Foundation websites, you should certainly do so now.
Fight Aging! suffered an aggressive comment spam attack last week that forced the hosting ISP to take the server down for a while. The problem with the version of MovableType that we were using (2.661) was that it will rebuild several static pages after each comment - so a few hundred comments over a short period of time will bury the server. The very useful MT-Blacklist was installed, but that particular version is no protection against unrecognized, new spam URLs.
There are numerous ways of dealing with this, but I decided to upgrade to the latest version of MovableType and MT-Blacklist. The anti-spam functionality is improved and I've configured the new software to deal with the rebuild problem. All comments issued to older posts are now held for moderation rather than being posted immediately. In addition - something I should have done a while back - I have shifted the location of the comment submission script to a new, non-standard location.
We'll see if all that helps. In the meanwhile, you folks shouldn't see any differences on the site - but do let me know if you run into anything that looks like an upgrade bug.
The passage of Proposition 71 and the prospects of $300 million in public embryonic stem cell research funding each year for the next decade is having a widespread effect on the research community. It has spurred on similar efforts in New Jersey and Massachusetts, while prompting discussions in other states with large research establishments. The threat of companies and talent moving to California is taken seriously these days:
Prior to the passage of a $3 billion stem cell research initiative in California last month, the institutions of Houston's Texas Medical Center seemed guaranteed a pre-eminent position in the research field some feel will revolutionize medicine. Now the lure of all that Golden State seed money might draw research talent away from the Texas Gulf Coast.
"We're very concerned about losing research scientists who are interested in stem cell biology and medicine to California," comments Dr. James Willerson, a cardiologist and stem cell researcher. He's also the president-elect of the Texas Heart Institute and president of the University of Texas Health Science Center in Houston.
So, for better or worse, I think we'll be seeing much more public funding for embryonic stem cell research and related fields at the state level in the next few years.
Over at Reason Online, Ronald Bailey offers his thoughts on the stem cell paralysis therapy recently trialed in South Korea. Many observers are cautious: "I would be very skeptical of drawing any conclusions from one case with no [experimental] controls." So we take a wait and see attitude while encouraging research: "It may well turn out that adult stem cells are good treatments for certain diseases, umbilical cord stem cells work best for others, and embryonic stem cells are better at curing still different maladies. Contrary to the claims of bioconservatives, it is not either adult and umbilical cord stem cells or embryonic ones; for the sake of millions of suffering patients, it's necessary to forge ahead on all three fronts."
Betterhumans reports on attempts to understand how adult stem cells from bone marrow have worked as a therapy for heart damage in some studies. "We set out to confirm, using more stringent criteria, the very appealing strategy of using stem cells from bone marrow to regenerate cardiac muscle, but we found that they never become normal, mature muscle cells. It's clear that the transplanted cells aren't growing, as we once hoped, into heart cells. But they may stimulate growth of new blood vessels into the damaged regions or they may secrete growth factors that promote recovery." Early stage regenerative medicine is moving fast - I expect to see these sorts of questions answered in the next few years.
Mass High Tech reports on the $13 million A round funding landed by Sirtris Pharmaceuticals - it follows close on the heels of their seed funding earlier this year. Sirtris was founded by David Sinclair to investigate sirtuin enzymes and their role in the health and longevity benefits of calorie restriction. They are "attractive drug targets for metabolism, inflammation, cancer and neurodegeneration." More funding in this area is a good thing - greater understanding of the mechanisms of aging and metabolism should lead to a class of therapies that can extend healthy life span and reduce the risk of suffering age-related conditions. Venture capitalists tend to invest in clusters of related technologies, so we can hope to see similar efforts funded in the years ahead.
Wired asks how far stem cell research into regenerative medicine can go without using the technology of therapeutic cloning (also known as somatic cell nuclear transfer). Therapeutic cloning "will likely be a conduit to therapies, not therapies themselves, at least not until scientists develop much more efficient therapeutic cloning methods. 'The value of nuclear transfer is not for cell therapy, it's to do molecular research to figure out how genetic disease is manifest,' said Tom Okarma, CEO of Geron." Immune reaction to implanted stem cells is a big issue in current research - one that early regenerative therapies are sidestepping by culturing adult stem cells from the patient for reimplantation.
I mentioned the recent linking of psychological stress and shortened telomeres, but Randall Parker has a lot more information at FuturePundit. In particular, other ways in which short telomeres have been linked to aging and health risks:
For those of you asking "What are telomeres and why are they important?" here is the short version: Telomeres are caps on the ends of chromosomes. They are made up of a very simple repeating sequence of DNA. Every time a cell divides its telomere gets shortened. Eventually the telomere gets so short that somehow as a result the cell can no longer divide or can divide only slowly and with increasing genetic damage.
My guess on the study reported above is that the mechanism of telomere shortening the researchers are observing is that stress causes certain classes of cells to divide more rapidly. Keep in mind that not all cells divide. For example, most nerve and heart cells are what are called post-mitotic. They no longer go through mitotic cell division. But skin cells and the various types of adult stem cells divide. One major cause of aging is that adult stem cell reservoirs throughout the body go through so many divisions that their telomeres get too short and they can't divide very well to provide cells to do repair.
Evidence has previously been found linking telomere length to mortality risk. The length of telomeres in endothelial progenitor cells (a type of adult stem cell) is linked to increased risk of cardiovascular disease. So those cells would be logical candidates to check for telomere length in women who have been under sustained stress.
Also, see an earlier thread here for good commentary on telomeres and the prospects for making them longer in a safe, reliable fashion.